摘要:
Chemical Corn m u n icat ions NUMBER 8/1965 28 APRIL On the Biosynthesis of Crotonosine By L. J. HAYNES and K. L. STUART (University of the West Indies, Jamaica) and D. H. R. BARTON, D. S. BHAKUNI, and G. W. KIRBY (Imperial College, London, S. W.7) WE have recently established the constitution (I) for crotonosine.l According to biogenetic theory2 crotonosine and related die none^^-^ should be derived in Nature from coclaurine (11; R' =Me, R" = H) or N-methylcoclaurine. We have now confirmed this experimentally. ( f)-Coclaurine was labelled with tritium, as shown (11), by base-catalysed exchange in tritiated water.6 Degradation to anisic acid (64% of the total activity) established the uniformity of labelling. This precursor was fed to Croton linearis and the derived crotonosine (see Table) converted into diacetylcrotonosine which had the same molar activity.Reduction to the tetra- hydro-derivative, treatment with hot methanolic sodium hydroxide, and reacetylation gave inactive diacetyltetrahydrocrotonosine. Thus all the tri- tium was, as expected, a to the carbonyl group in crotonosine. In a similar experiment ( j-)- [2-14C]- phenylalanine was also incorporated (0.04%) into cro t onosine . Resolution of ( &- ) -00'-dibenzylcoclaurine, with dibenzoyltartaric acid, gave the (+)- and (-)- forms, [ X I ~ +24.5" and -26.5' (in chloroform). Hydrogenolysis gave (+)- and (-) -coclaurine hydrochloride, [aID + 13" and - 14' (in methanol). The chirality of the enantiomers was established by 0 a HO "*a methylation with formaldehyde-formic acid to give (-)- and (+)-N-methylcoclaurine, [a], -120" and +123" (in methanol) (lit.-122" and L. J. Haynes, K. L. Stuart, D. H. R. Barton, and G. W. Kirby, Proc. Chem. SOC., 1964, 261. K. Bernauer, Helv. Chim. Ada, 1963, 46, 1783. M. P. Cava, K. Nomura, R. H. Schlessinger, K. T. Buck, B. Douglas, R. F. Raffanf, and J. A. Weisbach, Chem. and B. Gilbert, M. E. A. Gilbert, M. M. de Oliveira, 0. Ribeiro, E. Wenkert, B. Wickberg, U. Hollstein, and H. Rapoport, Cf. G. W. Kirby and L. Ogunkoya, unpublished work. 2 D. H. R. Barton and T. Cohen, "Festschrift A. Stoll," Birkhauser, Basle, 1957, p. 117. Ind., 1964, 282. J . Amev. Chem. SOC., 1964, 86, 694.142 CHEMICAL COMMUNICATIONS + 124.) .7 As expected, (+)-coclaurine hydro- (-J-)-Norcoclaurine (I1 ; R’ = R” = H), labelled in chloride [absolute configuration (11)] gave (-)-N- the usual way, was a rather less efficient precursor methylcoclaurine of known8J’ absolute configura- of crotonosine than was ( -J- ) -coclaurine.This tion. Feeding experiments with the labelled suggests, but does not prove, that demethylation of Incorporation of coclaurine derivatives into crotonosine Precursor ( j- )-Coclaurine ( 4- ) -Coclaurine ( - )-Coclaurine ( j- )-Norcoclaurine ( f )-Isococlaurine Incorporation (yo) 0.19, 0.20, 0.11” 0.17** O.OO**, 0*00** 0.08, 0.11, 0.07 040* Incorporations are corrected for loss of one tritium; * and ** indicate feeding experiments performed in parallel. enantiomers (as above) showed that only (+)- coclaurine does not precede incorporation. The coclaurine was an efficient precursor of crotonosine lack of incorporation of isococlaurine (11; R’ = H, (see Table). This confirms the absolute configura- R” = Me) supports this idea. Experiments are tion of crotonosine (see Cava et aZ., Zoc. cit.) and in hand ‘to test the possibilitylO of a methyl shows that the biological conversion is stereo- migration during crotonosine biosynthesis. specific. (Received, March 26th, 1965.) 7H. Yamaguchi, J . Pharm. SOC. Japan, 1958, 78, 678. 8 C. Ferrari and V. Deulofeu, Tetrahedron, 1962, 18, 419. 9 M. Tomita and J-I. Kunitomo, J . Pharm. SOC. Japan, 1962, 82, 734. 10 D. H. 13. Barton, Pure Appl. Chem., 1964, 9, 35.
ISSN:0009-241X
DOI:10.1039/C19650000141
出版商:RSC
年代:1965
数据来源: RSC