Organic Chemistry

A Unified and Bio-inspired Total Syntheses of Cochlearol B and Ganocins A-C via a Cyclobutane as Overbred Intermedi-ate



Cochlearol B and Ganocins A-C are polycyclic meroterpenoids isolated from Ganoderma cochlear with renoprotective effect and as AChE inhibitor, respectively. Using a strained cyclobutane as overbred intermediate, a unified synthesis of the four natural products is reported, including a scalable eight-step synthesis of cochlearol B. The synthesis of cochle-arol B features a [2+2] photocycloaddition to forge a highly substituted cyclobutane, and the first-generation synthesis of ganocin A features a complex carbocation rearrangement sequence initiated by an epoxide-opening. Moreover, a bio-inspired unprecedent oxidative cleavage of cyclobutane ring enables the second-generation synthesis of ganocin A ac-complished concisely in 10 steps. Furthermore, ganocins B and C were obtained after decarboxylation and a one pot re-action of -elimination, dehydration and deprotection. Our synthesis adds insight to the plausible non-enzymatic biogen-esis of these natural products.


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