The stereocontrolled total synthesis of altohyrtin A/spongistatin 1: the AB-spiroacetal segment

The convergent synthesis of the C1–C15 AB-spiroacetal subunit 2 of altohyrtin A/spongistatin 1 (1) is described. This highly stereocontrolled synthesis relies on matched boron aldol reactions of chiral methyl ketones, under Ipc₂BCl mediation, to establish the C5, C9 and C11 stereocentres, and formation of the desired thermodynamic spiroacetal under acidic conditions. The scalable synthetic sequence developed provided access to multi-gram quantities of 2, thus enabling the successful completion of the total synthesis of altohyrtin A/spongistatin 1, as reported in Part 4.