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A Cascade Strategy Enables a Total Synthesis of (±)-Morphine.

ABSTRACT: Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)-morphine that employs two key strategic cyclizations: 1) a diastereoselective light-mediated cyclization of an O-arylated butyrolactone to form a tricyclic cis-fused benzofuran and 2) a cascade ene-yne-ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6?%.

SUBMITTER: Chu S

PROVIDER: S-EPMC5129523 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A Cascade Strategy Enables a Total Synthesis of (±)-Morphine.

Chu Shuyu S Münster Niels N Balan Tudor T Smith Martin D MD

Angewandte Chemie (International ed. in English) 20161013 46

Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)-morphine that employs two key strategic cyclizations: 1) a diastereoselective light-mediated cyclization of an O-arylated butyrolactone to form a tricyclic cis-fused benzofuran and 2) a cascade ene-yne-ene ring closing metathesis to forge the tetracyclic morphine core. This approach e ...[more]

PMID: 27735107

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