The first total synthesis and absolute configuration assignment of protulactone A (1) has been achieved. Four stereoisomers, 1a, ent-1a, 1b, and ent-1b, of this natural polyketide were prepared by chiral pool synthesis starting from l- and d-arabinose, respectively. The absolute and relative configurations of all isomers were assigned by single-crystal X-ray analysis. Target compounds were screened for their in vitro cytotoxicity toward certain human tumor cells (NCI cancer cell line panel).
A divergent strategy for natural polyketides synthesis
has been
designed. This synthetic route allowed chemical alterations leading
to all stereoisomers of the natural agropyrenol 1, sordarial 2, and heterocornol B 4. Key steps involve desymmetrization
of divinylcarbinol using asymmetric Sharpless epoxidation and Heck
coupling of an easily available aromatic partner and prepared chiral
alkene. The versatility of the synthetic method was demonstrated on
the preparation of heterocornol A 3 and sordariol 5. The absolute and relative configurations of prepared natural
compounds 2·1/3C6H12 and 4 were confirmed and assigned by single-crystal X-ray analysis.
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