Total Synthesis of d,l-Saxitoxin

HETEROCYCLCS.V o l 14.No 10, 1 9 8 0 preferentially from the opposite side of the hydroxymethyl group resulting in the desired stereochemistry at the C-4 and C-5 positions.An alternative possibility was the acid-catalyzed cyclization of the urea 1.Assuming that rapid protonation- deprotonation would be followed by slow cyclization, the desired stereochemistry at the C-4 and C-5 positions might be expected.A possible disconnection of the urea 3 is shown in Scheme 3. In the first retrosynthetic step in this scheme, three carbon-nitrogen bonds and one vinylogous carbon-nitrogen bond were disconnected.Thus, we hoped that the urea 1 could be Scheme 3 constructed from four indicated fragments.One of the encouraging factors in this disconnection was that the necessary enamine 2 could be synthesized by adapting 4 the Eschenmoser procedure .The feasibility of the retrosynthesis described above was first tested in the C-12 deoxo series, simply because of the availability of the starting material.Thus, 2-pyrrolidinone (z) was converted to the vinylogous urethane 13 by using Eschenmoser's procedure except for step 3, which is a straightforward cleavage reaction of a 8-keto, Om-imino ester system under basic conditions.Treatment of the vinylogous urethane -13 with isocyanic acid in the presence of acetaldehyde in ether at room temperature yielded a product in excellent yield.This cyclization