52
A. -4.. BOTHNER-BY, R. S . SCHUTZ, R . F. DAWSON AND A I . L. SOLT
Vol. 84
I CONTRIBUTION FROM DEPARTMENT OF CHEMISTRY, HARVARD UNIVERSITY, CAMBRIDGE, MASS.,AND THE DEPARTMEXT OF
BOTAXY,COLUMBIA UNIVERSITY,
NEW YORK,
x. Y . ]
The Asymmetric Incorporation of Isotopic Label in the Biogenesis of Hyoscyamine BY A. A.BOTHNER-BY,~ R.S.SCHUTZ,3R.F. DAWSON AND >'I.L. SOLT RECEIVED JULY 31, 1961
The distribution of label in hyoscyamine biosynthesized by roots of Datura stramonium from acetate-l-C14was studied. One bridgehead carbon atom is labeled stereospecifically. -4symmetrical precursor, siich as nrriirs in the biosynthetic pathway for nicotine, thus does not occur in the pathway for hyoscyamine.
1ntroduc.tion.-Considerable evidence4-I3 has accumulated concerning the biosynthetic incorporation of labeled prxursors in the molecular skeletons of alkahids. It is now possible to state, e.g., that the pyrrolidine rings of nicotine (I) and of hyoscyamine (11) can arise from the ubiquitous amino acid metabolite, ornithine. Thus, Dewey, Byerrum and Ball,4 Leete,5 and Leete and Siegfried6have shown that when whole tobacco plants (Nicotiana tabacum L.) are grown on a medium containing ornithine-2-CI4 they produce nicotine labeled a t positions 2 and 5 of the pyrrolidine ring. I n similar experiments using Datura stramonium L., Leete, Marion and Spenser14 have demonstrated that ornithine-2-CI4 is incorporated into hyoscyamine biosynthetically, the C14 appearing as bridgehead carbon. When the alkaloid was degraded they did not, however, ascertain whether incorporation of label was asymmetric, i e . , whether all of the label appeared a t one of the two diastereoisomeric bridgehead positions. I n the case of nicotine i t seems clear that a symmetrical intermediate must occur somewhere in the pathway leading from ornithine. Leete has pointed out that incorporation of the label into positions 2 and 5 of the pyrrolidine ring of nicotine might occur through the intervention of some such intermediate as 111. In the case of anabasine (IV), Leete has demonstrated that the piperidine ring may be formed biosynthetically from lysine. When lysine-2-C14 is administered to whole plants of Yicotiana glauca Grah. anabasine is formed in which all of the (1) Abstracted from a thesis presented by R . S. Schutz t o Harvard University in partial fulfillment of t h e requirement for t h e degree of Doctor of Philosophy, April, 1959. ( 2 ) Present address: Rfellon Institute, 4400 Fifth Ave., Pittsburgh 13, P a (3) Present address: Yeshiva University, Amsterdam Ave., and '. 180th S t . , New York 33, N . I (4) J . L Dewey, I
