General Stereodivergent Enantioselective Total Synthetic Approach toward Macrosphelides A–G and M

A straightforward
enantioselective total synthesis algorithm for
the preparation of 8 out of 13 macrosphelides within 9–11 steps
starting from tert-butyl sorbate is presented. The
use of a cyclic sulfate as both protecting and reactivity directing
group is the key element within this algorithm. A high-pressure transesterification
allows for the selective ring-enlargement of the 15-membered macrosphelides
into the 16-membered counterparts. The absolute configurations of
the natural products were unambiguously assigned both by the chemical
synthesis and by X-ray structure analysis.