合成路线1

Chiral tetracyclic macrolactone (XXXVI): The condensation of the chiral aldehyde (XXV) with phosphonate (XXVI) in the usual way gives the nonatrienoic ester (XXVII), which is reduced with DIBAL to the corresponding alcohol and oxidized with MnO2 to the carbaldehyde (XXVIII). The condensation of (XXVIII) with the chiral oxazolidinone intermediate (VI) through its boron enolate yields the expected adduct (XXIX), which is reduced with Me4NBH(OAc)3 to afford the dihydroxy compound (XXX). The dethioacetalization of (XXX) by means of PhI(OCOCF3)2 in dichloromethane provides the cyclic ketal (XXXI). The regiocontrolled reduction of (XXXI) by means of NaBH4 in THF/water cleaves the chiral auxiliary to yield the carbinol (XXXII), which is successively oxidized with DMP and NaClO2 to afford the carboxylic acid (XXXIII) (1). The condensation of (XXXIII) with the chiral tripeptide intermediate (XV) by means of TBAF, HATU and DIEA in acetonitrile provides the corresponding amide (XXXIV), which is submitted to macrocyclization by means of LiOH, EDC and DIEA in dichloromethane to give the polycyclic macrolactone (XXXV). Finally, the Boc protecting group of (XXXV) is removed by means of Tms-OTf and lutidine in dichloromethane to afford the target chiral tetracyclic macrolactone (XXXVI)