Abstract. D-( + )-xylose has been converted to ( + )-sesbanimide A in sixteen steps. The synthetic scheme involves an unusual tricyclic siiylated derivative (9a) of the monobenzoylated product of the earlier described glutarimide intermediate (7). Compound 9a is a pivotal intermediate for the construction of ring C of ( + )-sesbanimide A.The alkaloid ( + )-sesbanimide A (12; Scheme 1) is one of the antileukemic constituents of the extracts of the seeds of Sesbania drumondii'. Syntheses of both ( + )-and ( -)-sesbanimide A have been reported from this2J-d and other laboratories''-k. A salient problem in all the reported syntheses is the selective protection of the secondary hydroxy group in diol intermediate 7. In our previous work2a,b this was achieved by a sequence of two steps involving acetalization with 3,4-dimethoxybenzaldehyde, followed by reductive ring opening of the actal function, to yield the C(5')-substituted 3,4-dimethoxybenzyl ether. Direct protection as a silyl ether, of the C(5')-hydroxyl function in derivatives of 7 in which the primary hydroxy had been derivatized, has been ~l a i m e d~' -~.~, though, in our opinion, without firm structural evidence. In our own work, we have shown that the silylation product of alcohol 8 is in fact the tricyclic lactam 9a2c,d. This structure is based upon detailed NMR studies and X-ray crystallographic analysis. We now describe in detail the total synthesis of ( + )-sesbanimide A via the crucial intermediate 9a. provided benzoate 8 in very good yield (94%). Attempted silylation of the free hydroxy group of 8 with tert-butyldiphenylsilyl triflate** led to a product whose structure was established as 9a. Of special relevance to the structure assignment of 9a were: (i) the presence of one ester carbonyl (1718 crn-') and one amide carbonyl(l668 cm-I), and the absence of the glutarimide carbonyls in the IR spectrum; (ii) a quarternary carbon at 6 101 ppm, in the I3C NMR spectrum, which has been assigned to the unique carbon (C-9), that is bonded to two oxygens and a nitrogen atom; (iii) the spatial proximity of C(7)-H to one of the C(12) protons and to N(1O)-H, as revealed by Nuclear Overhauser difference experiments and (iv) the X-ray structure' (Figure 1) of the alcohol 9b, obtained upon debenzoylation of 9a, by reduction with DIBAH*. The formation of 9a from 8 under the usual silylation conditions, presumably proceeds via attack of the C(5')-hydroxyl group on the C(2)-carbonyl function, which is activated by coordination with the silyl triflate or by addition of the same hydroxyl to the corresponding C(2)-0-silyl imino-ether", formed in the initial step of the reaction. In both cases the product (9a) possesses the 1 R,9S configuration at the newly created asymmetric centres. It should be noted that while operation of the aforementioned mechanism is, in principle also allowed at the C(6)-carbonyl, steric constraints, apparently, favour the ring closure leading to 9a, rather than a cyclisation to the isomeric 1S,9R tricyclic system 9c. The origin of this anomalous ...
