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.