It has been a long time between drinks. The main reason is that I have been busy and whenever I have any spare time I try to read up on the Zurich reformers, Huldrych Zwingli and Heinrich Bullinger. See my blog if you are interested: www.zurichconnection.blogspot.com.
One professor in Zurich wrote to me: “Du wärst problemlos in der Lage, so etwas zu schreiben”. That is, he thinks I have lots of spare time, especially for writing – it is really the reverse. 2010 was a very busy year. I also have virtually no access to the literature since I am no longer in chemistry and so it is hard to keep tabs on developments.
As far as I can see Anthony R. Carroll of Griffith University, Queensland, Australia, has not yet published his work on idiospermamine B C34H38N6 nor has J. B. Bremner (who was at Wollongong University, Australia) published his structure of the alkaloid isolated from Psychotria malayana. This alkaloid has a MW of 574 and I predict that it is C34H40N6.
However, I was able to access volume 63 of The Alkaloids: Chemistry and Biology. The following is summarized from the review of Yuen-Mun Choo and Teo-Seok Kam of the University of Malaya. Some of the material overlaps with what I have posted earlier but this review is more comprehensive:
Three calycanthine-type alkoaloids, (-)-calycanthine, (-)-isocalycanthine and meso-chimonanthine were isolated from Psychotria forsteriana from New Caledonia. This was the second time the levorotatory isomer of calycanthine was isolated after that isolated from Pausinystalia macroceras (Rubiaceae). It also represents the first isolation of meso-chimonanthine.
(-)-calycanthine and (+)-chimonanthine were also isolated from the skin of the Colombian poison dart frog, Phyllobates terribilis.
The aerial parts of Psychotria glomerulata from Panama afforded glomerulatine A ((8-8a), (8’-8’a)-tetradehydro-(-) calycanthine as the major alkaloid together with some glomerulatine B (8-8a), (8’-8a’)-tetradehydro-N’-demthyl-(-)calycanthine and (8-8a)-didehydro-(-)calycanthine.
Psychotria colorata afforded (8-8a), (8’-8’a)-tetradehydroisocalycanthine 3a (R) 3’a(R) as well as some (-)-calycanthine, isocalycanthine, (+)-chimonanthine, hodgkinsine and qudrigemine C.
(8-8a), (8’-8’a)-tetradehydroisocalycanthine 3a (R) 3’a(R) is identical to dehydrobhesine which together with bhesine ((8-8’a)-dehydroisocalycanthine) was isolated from the bark extract of the Malayan plant Bhesa paniculata.
The leaves of Argostemma yappii (Rubiaceae) from Indonesia gave (+)-isochimonanthine.
The seeds of chimonanthus praecox from Japan gave a new chimonanthine derivative, chimonanthidine (an extra NMe).
From Psychotria oleoides from New Caledonia were isolated three new tryptamine oligomers, qudrigemine C, isopsychotridine A and isopsychotridine B in addition to hodgkinsine and psychotridine.
From Calycodendron milnei from Vanuatu were isolated hodgkinsine and calycosidine.
A new tryptamine tetramer, psycholeine, was isolated from Psychotria oleoides using bioassay-guided fractionation. This is a meso-calycanthine subunit linked at C(7’) and C(7’’) to two N-methylpyrrolidinoindoline units.
A review of P. oleides and P. lyciiflora led to the isolation of new pyrrolidinoindoline alkaloids: Nb-demethly-meso-chimonanthine from P. lyciiflora and quadrigemine I, oleoidine and caledonine from P. oleides.
The review naturally mentions the isolation of idiopsermuline from the seeds of Idiospermum australiense by R.K. Duke et al from the Pharmacy Department of the University of Sydney. However, because my work has not been published there is no knowledge of my isolation of idiospermine.
A review of the Malaysian species, Psychotria rostrata, gave two new tryptamine oligomers: psychotrimine and psychopentamine.
Friday, December 31, 2010
Thursday, December 24, 2009
Idiospermine and idiospermamine
Of the calycanthaceous alkaloids identified to date, idiospermamine is the one that is closest biogenetically to idiospermine.
Idiospermamine can be envisaged as having been formed by coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by the formation of a pyrrolidine ring through the linking of the tetrahydroquinoline N to the alpha position of the N-methyltryptamine molecule and methylation of the N of the indole ring.
Idiospermine, on the other hand, can be envisaged as having been formed by the coupling of a calycanthine moiety (through a C para to a tetrahydroquinoline N, ie C6) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring (This may be regarded as analogous to the coupling in the formation of hodgkinsine and the quadrigemines which are followed by N-methylation, aryl migration and aromatization.).
I envisage the following related alkaloid might also one day be identified:
Coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring. This alkaloid might be termed idiospermine-B.
Idiospermamine can be envisaged as having been formed by coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by the formation of a pyrrolidine ring through the linking of the tetrahydroquinoline N to the alpha position of the N-methyltryptamine molecule and methylation of the N of the indole ring.
Idiospermine, on the other hand, can be envisaged as having been formed by the coupling of a calycanthine moiety (through a C para to a tetrahydroquinoline N, ie C6) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring (This may be regarded as analogous to the coupling in the formation of hodgkinsine and the quadrigemines which are followed by N-methylation, aryl migration and aromatization.).
I envisage the following related alkaloid might also one day be identified:
Coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring. This alkaloid might be termed idiospermine-B.
Saturday, December 19, 2009
Idiospermine and other biogenetically related alkaloids
Alkaloids biogenetically related to idiospermine have been isolated from sources other than plants. For example, (-)-calycanthine and (+)-chimonanthine have been isolated from the Columbian poisondart frog, Phyllobates terribilis. The communesins have been isolated from a strain of Penicillum sp. marine fungus while perophoramidine has been isolated from the fungus Perophora namei (Ascidiaceae).
A list of the alkaloids biogenetically related to idiospermine include:
• Calycanthine
• Chimonanthine
• Calycanthidine (a mono methylated derivative of chimonanthine)
• Folicanthine (a di methylated derivative of chimonanthine)
• Chimonanthidine (same as calycanthidine but with the third methyl on an indole N rather than an indolamine N)
• Hodgkisine (related to chimonanthine – consisting of three N-methyl tryptamine units)
• Qudrigemine (related to chimonanthine – consisting of four N- methyl tryptamine units)
• Idiosperumline (a mono methylated derivative of hodgkinsine)
• Psychotrimine (related to chimonanthine – consisting of three N-methyl tryptamine units with an indole N bonded to a C7 position of chimonanthine)
• Psychopentamine (related to chimonanthine – consisting of five N-methyl tryptamine units with an indole N bonded to a C7 position of chimonanthine)
• Idiospermamine (consisting of three N-methyl tryptamine units with a calycanthine moiety attached to a beta position of an N-methyl tryptamine unit followed by cyclisation to form a pyrrolidine ring)
• Calycosidine (consisting of a calycanthine moiety attached to a pyrrolidinoindole moiety)
• Psycholeine (consisting of a calycanthine moiety attached to a pyrrolidinoindole moiety at each of the C8 positions)
• Psychotridine (consisting of five N-methyl tryptamine units)
• Isopsychotridine (consisting of five N-methyl tryptamine units)
• Vatine and Vatine-A (both consisting of six N-methyl tryptamine units)
• Vatamine (consisting of seven N-methyl tryptamine units)
• Vatamidine (consisting of eight N-methyl tryptamine units)
• Perophoramidine
• CPC-2
A helpful overview of the biogenesis of these alkaloids may be found in Jeremy A. May and Brian Stoltz, “The structural and synthetic implications of the biosynthesis of the calycanthaceous alkaloids, the communesins and nomofungin”, Tetrahedron, vol. 62 (2006), pp5262-5271.
A list of the alkaloids biogenetically related to idiospermine include:
• Calycanthine
• Chimonanthine
• Calycanthidine (a mono methylated derivative of chimonanthine)
• Folicanthine (a di methylated derivative of chimonanthine)
• Chimonanthidine (same as calycanthidine but with the third methyl on an indole N rather than an indolamine N)
• Hodgkisine (related to chimonanthine – consisting of three N-methyl tryptamine units)
• Qudrigemine (related to chimonanthine – consisting of four N- methyl tryptamine units)
• Idiosperumline (a mono methylated derivative of hodgkinsine)
• Psychotrimine (related to chimonanthine – consisting of three N-methyl tryptamine units with an indole N bonded to a C7 position of chimonanthine)
• Psychopentamine (related to chimonanthine – consisting of five N-methyl tryptamine units with an indole N bonded to a C7 position of chimonanthine)
• Idiospermamine (consisting of three N-methyl tryptamine units with a calycanthine moiety attached to a beta position of an N-methyl tryptamine unit followed by cyclisation to form a pyrrolidine ring)
• Calycosidine (consisting of a calycanthine moiety attached to a pyrrolidinoindole moiety)
• Psycholeine (consisting of a calycanthine moiety attached to a pyrrolidinoindole moiety at each of the C8 positions)
• Psychotridine (consisting of five N-methyl tryptamine units)
• Isopsychotridine (consisting of five N-methyl tryptamine units)
• Vatine and Vatine-A (both consisting of six N-methyl tryptamine units)
• Vatamine (consisting of seven N-methyl tryptamine units)
• Vatamidine (consisting of eight N-methyl tryptamine units)
• Perophoramidine
• CPC-2
A helpful overview of the biogenesis of these alkaloids may be found in Jeremy A. May and Brian Stoltz, “The structural and synthetic implications of the biosynthesis of the calycanthaceous alkaloids, the communesins and nomofungin”, Tetrahedron, vol. 62 (2006), pp5262-5271.
Monday, December 14, 2009
The chemical constituents of Idiospermum australiense (Diels) S.T. Blake – Part 2
In the first post I discussed the alkaloids that were extracted from the plant. A subsequent post discussed the structure of a new triterpene lactone that was extracted. This post will discuss the other substances that were identified from the plant.
Of the substances that merit mention -
The bark afforded:
The coumarin scopoletin 1.0%
The flavone glycoside hesperidin 2.0%
β-sitosterol 0.01%
The seeds or cotyledons afforded:
Hesperidin 0.5%
Scopoletin 0.2%
p-hydroxybenzaldehyde 0.05%
The wood afforded:
The flavone hesperetin 0.05%
Scopoletin 0.14%
Scopoletin methyl ether 0.03%
The leaves afforded:
Hesperetin 0.05%
The flavone diosmetin 1.5 x 10-3%
The flavone acacetin 1.5 x 10-3%
A sesquiterpene hydrocarbon (C15H24) 0.38%
Because of time constraints, further investigative work on the sesquiterpene hydrocarbon was not carried out.
The Australian researchers, Brophy and Goldsack have examined the essential oils in Idiospermum australiense. Their results are as follows:
The leaf essential oil obtained from Idiospermum australiense (Diels) S. T. Blake in 0.3-0.5% yield (based on fresh weight) consisted of monoterpenes and sesquiterpenes. Of the 41 compounds detected in amounts >0.05%, the principal components were bicyclogermacrene (48%) and caryophyllene (8%). The tricyclic sesquiterpene alcohols globulol, viridiflorol and spathulenol were also present each in approximately 5% amounts – Jospeh J. Brophy and Robert J. Goldsack Flavour and Fragrance Journal, vol. 7 (1992), pp79-80).
Both bicyclogermacrene and caryophyllene are sesquiterpenes with the molecular formula C15H24.
D.A. Young and R.W. Sterner, Biochem. Syst. Ecol.vol. 9 (1981), p185 have examined the flavonoids in the leaves of Idiospermum australiense. Their results are cited by Robert Hegenauer in his “Chemotxonomie der Pflanzen: eine Übersicht über die Verbreitung und die sysstematische Bedeutung der Pflanzenstoffe” vol. VIII on p109. Hegenauer notes that Young and Sterner refer to the presence of 7-glucosides of luteolin and apigenin.
Our results revealed the presence of the 7- glycoside, hesperidin, and its aglycone hesperetin together with diosmetin and acacetin. Diosmetin is a methyl derivative of luteolin while acacetin is a methyl derivative of apigenin. Hesperetin is the flavanone from diosmetin.
Of the substances that merit mention -
The bark afforded:
The coumarin scopoletin 1.0%
The flavone glycoside hesperidin 2.0%
β-sitosterol 0.01%
The seeds or cotyledons afforded:
Hesperidin 0.5%
Scopoletin 0.2%
p-hydroxybenzaldehyde 0.05%
The wood afforded:
The flavone hesperetin 0.05%
Scopoletin 0.14%
Scopoletin methyl ether 0.03%
The leaves afforded:
Hesperetin 0.05%
The flavone diosmetin 1.5 x 10-3%
The flavone acacetin 1.5 x 10-3%
A sesquiterpene hydrocarbon (C15H24) 0.38%
Because of time constraints, further investigative work on the sesquiterpene hydrocarbon was not carried out.
The Australian researchers, Brophy and Goldsack have examined the essential oils in Idiospermum australiense. Their results are as follows:
The leaf essential oil obtained from Idiospermum australiense (Diels) S. T. Blake in 0.3-0.5% yield (based on fresh weight) consisted of monoterpenes and sesquiterpenes. Of the 41 compounds detected in amounts >0.05%, the principal components were bicyclogermacrene (48%) and caryophyllene (8%). The tricyclic sesquiterpene alcohols globulol, viridiflorol and spathulenol were also present each in approximately 5% amounts – Jospeh J. Brophy and Robert J. Goldsack Flavour and Fragrance Journal, vol. 7 (1992), pp79-80).
Both bicyclogermacrene and caryophyllene are sesquiterpenes with the molecular formula C15H24.
D.A. Young and R.W. Sterner, Biochem. Syst. Ecol.vol. 9 (1981), p185 have examined the flavonoids in the leaves of Idiospermum australiense. Their results are cited by Robert Hegenauer in his “Chemotxonomie der Pflanzen: eine Übersicht über die Verbreitung und die sysstematische Bedeutung der Pflanzenstoffe” vol. VIII on p109. Hegenauer notes that Young and Sterner refer to the presence of 7-glucosides of luteolin and apigenin.
Our results revealed the presence of the 7- glycoside, hesperidin, and its aglycone hesperetin together with diosmetin and acacetin. Diosmetin is a methyl derivative of luteolin while acacetin is a methyl derivative of apigenin. Hesperetin is the flavanone from diosmetin.
Sunday, December 13, 2009
Idiospermuline and idiospermamine – other tryptamine trimers from Idiospermum australiense
In an earlier post reference was made to both idiospermuline and idiospermamine.
Idiospermuline was isolated from the seeds of Idiospermum australiense by researchers from the Department of Pharmacology of the University of Sydney (Rujee K. Duke, Robin D. Allan, Graham A. R. Johnston, Kenneth N. Mewett and Ann D. Mitrovic, “Idiospermuline, a trimeric pyrrolidinoindoline alkaloid from the seed of Idiospermum australiense, Journal of Natural Products, vol. 58 (1995), pp1200-1208).
(-)-Idiospermuline was isolated form the seeds of the plant together with (+)-calycanthine and (-)-chimonanthine. Idiospermuline is a chimonanthine derivative and may be viewed as consisting of a chimonanthine moiety coupled via its C7’ carbon atom to the C3a” carbon atom of a pyrrolidinoindole moiety. In overall terms it is formally a dimethylated derivative of hodgkinsine, an alkaloid from Hodgkinsonia frutescens F. Muell (Rubiaceae) – A.A. Gorman, M. Hesse, H. Schmidt, P.G. Waser and W.H. Hopff in The Alkaloids, vol. 1, p203 (The Chemical Society: London 1971). Hogkinsine is also isolated from Psychotria sp.
The Overman group have made an enantioselective synthesis of (-)-idiospermuline (Tetrahedron, vol. 59 (2003), pp6905-6919).
Idiospermuline (C35H42N6) has only one secondary nitrogen atom and has a molecular weight of 546.
Idiospermamine B, on the other hand (C34H38N6, see an earlier post) has two secondary nitrogen atoms.
J.B. Bremner has reported two new alkaloids from Psychotria malayana Jack (Surya Hadi and John B. Bremner, Initial Studies on Alkaloids from Lombok Medicinal Plants, Molecules, vol. 6 (2001), pp117-129). From the plant Bremner and his colleague isolated hodgkinsine (C33H38N6, M.W. 518), chimonanthine and two other alkaloids with molecular weights of 186 and 574.
I wonder if it is possible that the alkaloid with M.W. of 574 isolated by Bremner is a trimethylated derivative of idiospermine (C34H40N6)?
Idiospermuline was isolated from the seeds of Idiospermum australiense by researchers from the Department of Pharmacology of the University of Sydney (Rujee K. Duke, Robin D. Allan, Graham A. R. Johnston, Kenneth N. Mewett and Ann D. Mitrovic, “Idiospermuline, a trimeric pyrrolidinoindoline alkaloid from the seed of Idiospermum australiense, Journal of Natural Products, vol. 58 (1995), pp1200-1208).
(-)-Idiospermuline was isolated form the seeds of the plant together with (+)-calycanthine and (-)-chimonanthine. Idiospermuline is a chimonanthine derivative and may be viewed as consisting of a chimonanthine moiety coupled via its C7’ carbon atom to the C3a” carbon atom of a pyrrolidinoindole moiety. In overall terms it is formally a dimethylated derivative of hodgkinsine, an alkaloid from Hodgkinsonia frutescens F. Muell (Rubiaceae) – A.A. Gorman, M. Hesse, H. Schmidt, P.G. Waser and W.H. Hopff in The Alkaloids, vol. 1, p203 (The Chemical Society: London 1971). Hogkinsine is also isolated from Psychotria sp.
The Overman group have made an enantioselective synthesis of (-)-idiospermuline (Tetrahedron, vol. 59 (2003), pp6905-6919).
Idiospermuline (C35H42N6) has only one secondary nitrogen atom and has a molecular weight of 546.
Idiospermamine B, on the other hand (C34H38N6, see an earlier post) has two secondary nitrogen atoms.
J.B. Bremner has reported two new alkaloids from Psychotria malayana Jack (Surya Hadi and John B. Bremner, Initial Studies on Alkaloids from Lombok Medicinal Plants, Molecules, vol. 6 (2001), pp117-129). From the plant Bremner and his colleague isolated hodgkinsine (C33H38N6, M.W. 518), chimonanthine and two other alkaloids with molecular weights of 186 and 574.
I wonder if it is possible that the alkaloid with M.W. of 574 isolated by Bremner is a trimethylated derivative of idiospermine (C34H40N6)?
The degradation of idiospermolide
An earlier post described the degradation of idiospermolide to 29-norcycloartanol. This post gives the experimental and spectral data for the intermediate degradation products.
Ring opening of idiopsermolide with potassium t-butoxide:
After reacting idiospermolide with potassium t-butoxide in t-butanol the crude diene acid (λmax 265 nm) was methylated with diazomethane to give the diene ester which crystallized from methanol as colourless needles, m.p. 149-150° (Found: C: 79.7%; H: 9.8%. C30H46O3 requires C: 79.7%; H: 9.7%). νmax 1705, 1636, 1602, 1451, 1432, 1235, 1200, 1170, 1113, 985 cm-1; λmax 268, nm, ε 25000; mass spectrum (452, (P,22), 420 (30), 326 (12), 299 (90), 292 (70), 283 (12), 281 (14), 257 (16), 229 (18), 215 (20), 203 (28), 189 (64), 175 (80), 154 (100),149 (60), 147 (70), 145 (46), 135 (62), 133 (80)).
Hydrogenation of the diene ester:
The diene ester was hydrogenated with palladium/charcoal to give the saturated ester which crystallized from methanol as colourless prisms, m.p. 83-5-85° (Found: M.W. 456.360 ± 0.003. C30H48O3 requires M.W. 456.3603). νmax 1730, 1708, 1202 cm-1; mass spectrum 456, (P, 53), 441 (21), 425 (7), 409 (10),328 (21), 299 (66), 251 (17), 175 (28), 121 (45), 107 (52), 95 (75), 81 (52), 55 (100).
Conversion of the hydrogenated ester to 29-norcycloartanol:
The ester was reduced with lithium aluminium hydride and the crude diol tosylated with p-toluenesulphonyl chloride. The crude tosylate was reduced with lithium aluminium hydride to produce 29-cycloartanol which crystallized from methanol as colourless needles, m.p. 127-130° (lit. 128-132° G. Berti, F. Bottari, A. Marsili, I. Morelli and M. Palvani, Tetrahedron Lett., 1967, p125), νmax 3700-3300, 1200, 1120 cm-1; mass spectrum: 414 (P,5), 412 (4), 399 (20), 397 (14), 396 (18), 381 (24), 121 (46), 119 (42), 109 (52), 107 (64), 105 (56), 95 (74), 93 (56), 91 (52), 81 (76), 79 (50), 69 (76), 67 (52), 57 (84), 55 (100).
Conversion of cycloeucalenol to 29-norcycloartanol:
The acetate of cycloeucalenol was ozonlyzed to give demethyloxocycloeucalenyl acetate. This was reduced with sodium borohydride, tosylated with p-toluenesulphonyl chloride and then reduced with lithium aluminium hydride. The product was identical with the 29-norcycloartanol prepared via degradation of idiospermolide: the mixed m.p. was undepressed and the i.r. spectra were identical.
Ring opening of idiopsermolide with potassium t-butoxide:
After reacting idiospermolide with potassium t-butoxide in t-butanol the crude diene acid (λmax 265 nm) was methylated with diazomethane to give the diene ester which crystallized from methanol as colourless needles, m.p. 149-150° (Found: C: 79.7%; H: 9.8%. C30H46O3 requires C: 79.7%; H: 9.7%). νmax 1705, 1636, 1602, 1451, 1432, 1235, 1200, 1170, 1113, 985 cm-1; λmax 268, nm, ε 25000; mass spectrum (452, (P,22), 420 (30), 326 (12), 299 (90), 292 (70), 283 (12), 281 (14), 257 (16), 229 (18), 215 (20), 203 (28), 189 (64), 175 (80), 154 (100),149 (60), 147 (70), 145 (46), 135 (62), 133 (80)).
Hydrogenation of the diene ester:
The diene ester was hydrogenated with palladium/charcoal to give the saturated ester which crystallized from methanol as colourless prisms, m.p. 83-5-85° (Found: M.W. 456.360 ± 0.003. C30H48O3 requires M.W. 456.3603). νmax 1730, 1708, 1202 cm-1; mass spectrum 456, (P, 53), 441 (21), 425 (7), 409 (10),328 (21), 299 (66), 251 (17), 175 (28), 121 (45), 107 (52), 95 (75), 81 (52), 55 (100).
Conversion of the hydrogenated ester to 29-norcycloartanol:
The ester was reduced with lithium aluminium hydride and the crude diol tosylated with p-toluenesulphonyl chloride. The crude tosylate was reduced with lithium aluminium hydride to produce 29-cycloartanol which crystallized from methanol as colourless needles, m.p. 127-130° (lit. 128-132° G. Berti, F. Bottari, A. Marsili, I. Morelli and M. Palvani, Tetrahedron Lett., 1967, p125), νmax 3700-3300, 1200, 1120 cm-1; mass spectrum: 414 (P,5), 412 (4), 399 (20), 397 (14), 396 (18), 381 (24), 121 (46), 119 (42), 109 (52), 107 (64), 105 (56), 95 (74), 93 (56), 91 (52), 81 (76), 79 (50), 69 (76), 67 (52), 57 (84), 55 (100).
Conversion of cycloeucalenol to 29-norcycloartanol:
The acetate of cycloeucalenol was ozonlyzed to give demethyloxocycloeucalenyl acetate. This was reduced with sodium borohydride, tosylated with p-toluenesulphonyl chloride and then reduced with lithium aluminium hydride. The product was identical with the 29-norcycloartanol prepared via degradation of idiospermolide: the mixed m.p. was undepressed and the i.r. spectra were identical.
Wednesday, December 9, 2009
The mono-ethylenethioketal derivative of idiospermolide
The n.m.r spectrum of the mono-ethylenethioketal derivative of idiospermolide revealed that under the acidic reaction conditions the cyclcopropane ring had opened to give a compound with a 9,11 double bond. 9,19-cyclotriterpenoids are known to cleave predominantly to the Δ9(11) isomer under acid treatment (G. Ourisson, P. Crabbé and O.R. Rodig, Tetracyclic Triterpenes (Herman: Paris 1964)).
Apart from the broad doublet at δ 6.61 (J 6 Hz) for C24-H and the broad doublet at δ 4.47 (J 13 Hz) for C22-H, the characteristic features of the n.m.r. spectrum were a broad doublet at δ 5.30 (J 5Hz) for C11-H, as four proton singlet at δ 3.22 for the ethylenedithioketal protons, a singlet at δ 0.72 for C14-Me and a singlet at δ 0.66 for C13-Me. The signals for C13-Me and C14-Me were assigned by comparison with the signals for C13-Me and C14-Me in grandisolide (J.P. Kutney, D.S. Grierson, G.D. Knowles, N.D. Westcott and I.H. Rogers, Tetrahedron, 1973, vol. 29, p13); the chemical shift of C11-H at δ 5.30 is characteristic of Δ9(11) triterpenoids.
The other signals of the n.m.r. spectrum were consistent with the structure proposed and were assigned as follows:
Broad singlet, 3H, δ 1.90 C25-Me
Doublet, 3H, δ 1.15, C4-Me (J 7 Hz)
Singlet, 3H, δ 0.98, C10-Me
Doublet, 3H, δ 0.96, C20-Me (J 7 Hz)
Multiplet, 21H, the remaining protons
Studies with the shift reagent Eu(dpm)3 gave further information. The reagent apparently bonded to the lactone carbonyl. For a 5.9 x 10-5M chloroform solution of the ethylenethioketal which was 1.8 x 10-5 M with respect to Eu(dpm)3, the following shifts were observed:
Doublet, δ 7.05, C24-H (J 6 Hz)
Singlet, δ 2.75, C25-Me
Doublet, δ 1.15, C4-Me (J 7 Hz)
Doublet, δ 1.11, C20-Me (J 7 Hz)
Singlet, δ 0.98, C10-Me
Singlet, δ 0.79, C14-Me
Singlet, δ 0.67, C13-Me
Apart from the broad doublet at δ 6.61 (J 6 Hz) for C24-H and the broad doublet at δ 4.47 (J 13 Hz) for C22-H, the characteristic features of the n.m.r. spectrum were a broad doublet at δ 5.30 (J 5Hz) for C11-H, as four proton singlet at δ 3.22 for the ethylenedithioketal protons, a singlet at δ 0.72 for C14-Me and a singlet at δ 0.66 for C13-Me. The signals for C13-Me and C14-Me were assigned by comparison with the signals for C13-Me and C14-Me in grandisolide (J.P. Kutney, D.S. Grierson, G.D. Knowles, N.D. Westcott and I.H. Rogers, Tetrahedron, 1973, vol. 29, p13); the chemical shift of C11-H at δ 5.30 is characteristic of Δ9(11) triterpenoids.
The other signals of the n.m.r. spectrum were consistent with the structure proposed and were assigned as follows:
Broad singlet, 3H, δ 1.90 C25-Me
Doublet, 3H, δ 1.15, C4-Me (J 7 Hz)
Singlet, 3H, δ 0.98, C10-Me
Doublet, 3H, δ 0.96, C20-Me (J 7 Hz)
Multiplet, 21H, the remaining protons
Studies with the shift reagent Eu(dpm)3 gave further information. The reagent apparently bonded to the lactone carbonyl. For a 5.9 x 10-5M chloroform solution of the ethylenethioketal which was 1.8 x 10-5 M with respect to Eu(dpm)3, the following shifts were observed:
Doublet, δ 7.05, C24-H (J 6 Hz)
Singlet, δ 2.75, C25-Me
Doublet, δ 1.15, C4-Me (J 7 Hz)
Doublet, δ 1.11, C20-Me (J 7 Hz)
Singlet, δ 0.98, C10-Me
Singlet, δ 0.79, C14-Me
Singlet, δ 0.67, C13-Me
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