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Most Requested Journal Articles 1Q07-Chemistry and Related Science
Following is one of the journal articles most requested by researchers using CAS electronic products.
CAPLUS COPYRIGHT 2007 ACS on STN
Concise total syntheses of the cytotoxic marine natural products amphidinolide X (I) and amphidinolide Y (II), as well as of the non-natural analog 19-epi-amphidinolide X, are described. A pivotal step of the highly convergent routes to these structurally rather unusual secondary metabolites consists of a syn-selective formation of allenol III by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide IV (derived from a Sharpless epoxidn.) with a Grignard reagent. Allenol III was then cyclized with the aid of Ag(I) to give dihydrofuran V contg. the (R)-configured tetrasubstituted sp3 chiral center at C19, which was further elaborated into THF VI representing the common heterocyclic motif of I and II. The aliph. chain of amphidinolide X featuring an anti-configured stereodiad at C10 and C11 was generated by a palladium-catalyzed, Et2Zn-promoted addn. of the enantiopure propargyl mesylate VII to the functionalized aldehyde VIII. The prepn. of the corresponding C1-C12 segment of amphidinolide Y relies on asym. hydrogenation of an .alpha.-ketoester, a diastereoselective boron aldol reaction, and a chelate-controlled addn. of MeMgBr in combination with suitable oxidn. state management for the elaboration of the tertiary acyloin motif. Importantly, the end games of both total syntheses follow similar blueprints, involving key fragment coupling processes via the "9-MeO-9-BBN" variant of the alkyl-Suzuki reaction and final Yamaguchi esterifications to forge the 16-membered macrodiolide ring of amphidinolide X and the 17-membered macrolide frame of amphidinolide Y, resp. This methodol. convergence ensures high efficiency and an excellent overall economy of steps for the entire synthesis campaign. Updated 5/15/2007 1:15:16 PM
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