Asymmetric aldol-like reactions of cinnamaldehyde, dienal 3 (fragment C7-Cl2 of macro-Iactin A), and dienal 4 (fragment C15-C24) with (i) chiral acetylthiazolidinethione-derived enolates, (ii) chiral boron enolates, and (iii) silyl enolates in the presence of chiral titanium-2,2'-dinaphthol complexes are compared. Use of the thiazolidinethione auxiliary and Tic4 shows practical advantages; e.g., C5-Cl2 fragment 7 has been isolated enantiomerically pure in 74% yield. Copyright 8 1996 Elsevie! Science Ltd Macrolactin A (l), the parent aglycone of a novel family of 24-membered polyene macrolides isolated by Fenical et al.' from a deep sea bacterium, shows significant inhibition of mammalian Herpes simplex viruses and protects T-lymphoblast cells against human HIV viral replication, among other interesting properties.1 Approaches to some fragments of 1 have been already reported. 2 Very recently, Boyce and Pattenden have achieved the cyclisation, via an intramolecular Stille coupling, of a protected precursor.3 This has prompted us
to advance here our work in connection with a different enantioselective total synthesis of 1 and its congeners.
Our strategy is summa&d in Scheme 1. The Z, E conjugate double bonds were envisaged to be built up by appropriate C,$-C,,2 couplings (disconnections C9-ClO and C3-C4, not drawn in Scheme 1) and the E, E