Jan. 20, 1959
COMMUNICATIONS TO THE EDITOR
ring homolog (1710 ~ m . - l ) . ~This is an indication of interaction of the sulfur electrons with the carbonyl increasing the dipolar character of the carbonyl and is similar to what has been observed in the nitrogen ~ y s t e r n . ~I11 was reduced with lithium aluminum hydride to give I, 50%; b.p. 78-80' (2 mm.), n20D 1.5379, m.p. 29-29.5; mnitrobenzenesulfonate, C, 46.97; H, 5.34; 5acetoxythiacyclooctane- 1,1-dioxide, C, 49.12 ; H, 7.35; S, 14.49. Work is in progress to determine the scope of these novel transannular effects with sulfur.
507
'ix, ' CHd '
IIa, R IIb, R IIc, R IId, R IIe, R
= =
kR CO-NHCH~CH~C~H~-~,~(OCHB)Z COOCHz, A'',''
= COOCHa = =
CHzOH CHI
and (ii) in agreement with the results of Preobrazhenskii, et ~ l .and, , ~ more recently, Battersby and but contrary to those of Brossi, et a1.* I I a is convertible to emetine and isoemetine (C-1 epimer of emetine). Further, the assigment of stereochemistry of I I a and IIc, originally made* only by analogy to certain reduction results obDEPARTMEXT OF CHEMISTRY C. G. OVERBERGER tained in this Laboratory,la now has been validated: lithium aluminum hydride reduction of IIc POLYTECHNIC INSTITUTE OF BROOKLYX BROOKLYN, NEWYORK k N 0 LUSI' produced an alcohol (IId) identical with that obRECEIVED DECEMBER 4, 1958 tained through another route by Burgstahler and B i t h o ~ ,who ~ , ~ related their material to the oxygen-free base IIe; the stereochemistry (11) of the THE STEREOCHEMISTRY OF THE IPECAC latter had been established previously. la These ALKALOID EMETINE findings complement those of B a t t e r ~ b yand ~ ~fully Sir: corroborate the original proposal Ia. The original proposal1 of stereoformula Ia (I, Despite inferences to the contrary,* the relative Airz) for emetine (I, R = CH,) and related ipecac configuration of C-1 in emetine has not been assigned, and so far there has not appeared any eviC " O m dence bearing on this point. A simple approach C H O +k< , 1 to this unwieldy problem is based upon the structural similarity of the two tetrahydroisoquinoline rings, each with an asymmetric center in the prox+hI3 imity of an ultraviolet chromophore.7 In the stereoisomer where C-1 and C-1' are "antipodal" (I),the H ~ ~ O C H J optical contributions of the two asymmetric centers might be expected approximately to cancel each OR I other and cause a negligible rotational change in the alkaloids was challenged recently by Brossi, Co- range 300-700 mp. In the case where the absolute hen, Osbond, Plattner, Schnider and Wickens,2 who configurations are the same, the optical effects advanced an alternative structure in which C-1' should be reinforced, and the normal change of possesses the epimeric, less stable configuration. rotation with wave length should prevail. ExThe modification was occasioned by the belief of perimentally, in the region 350-700 mp, the slightly Brossi, et al., that Bischler-Napieralski cyclization positive rotation of emetine hydrobromide remains and reduction of the tricyclic amide IIa led to two virtually constant, falling off to negative values bediastereoisomers of emetine; this report contradicts low 350 m,u; in contrast, isoernctine hydrobromide exhibits gradually increasing positive rotation that of the earlier Russian investigators, whose statement that emetine resulted from this reaction down to 300 mp, followed by a sharp decline to sequence provided part of the basis for our pro- negative rotations below 300 nip.* OF CHEMISTRY posal. Reinvestigation of the pertinent reactions DEPARTMENT UNIVERSITY OF TTTISCONSIS EUGENE E. V A N TAMELEN reveals that (i) catalytic hydrogenation of the AI' MADISON, TYISCOXSIN JACKSOS U. HESTER, JR. precursor (IIb) gives rise to a high yield of saturated RECEIVED DECEMBER 8, 195s _ _ _ _ _ tricyclic ester IIc) the only detectable stereoisomer, (3) C. G. Overberger and A. Iiatchman, THIS JOURNAL, 78, 1965 (1956). (1) X. J. Leonard, M . Oki, J. Broder and H. Boaz, i b i d . , 7 7 , 6237 (1955), and earlier papers. ( 5 ) A portion of thesis submitted b y A. Lusi in partial fulfillment of t h e degree of Master of Science in t h e Graduate School of t h e Polytechnic Institute of Brooklyn.
(1) (a) E. E. van Tamelen, P. E. Aldrich and J. B. Hester, Jr., THIS JOURNAL,79, 4817 (1957); (b) c j . A. R. Battersby, R. Binks, D. Davidson, G. C. Davidson and T. P. Edwards, Chent. a n d I d . , 982 (1957); A. R. Battersby a n d S. Cox, ibid., 983 (1957). (2) A. Brossi, A. Cohen, J. &I. Osbond, P1. A. Plattner, 0. Scbnider and J. C. Wickens, i b i d . , 491 (1958). (3) N. A. Preobrazhenskii, R. P. Evstigneeva, R. S. Livshits a n d K. M. Fedyuohkina, D o k l a d y A c a d . X a u k , U S S R ,81, 421 (1951).
(4) (a) A . R. Battersby and J. C. Turner, Chem. ami I d , , 1824 (1958); (b) 4 . R. Battersby, i b i d . , 1324 (1958). ( 5 ) T h e authors are indebted t o Professor Burgstahler fur his cooperation in carrying out t h e identification of this substance. ( 6 ) A. W. Burgstahler and 2. J. Bitbos, THIS J O U R N A L , 81, 503 (1959). (7) See C. Djerassi, Bull. SOC. chim. F r a n ~ e741 (1957). (8) We are grateful t o Professor Carl Djerassi for supplying the optical rotatory dispersion data.
