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Volumn 118, Issue 47, 1996, Pages 11759-11770

Total synthesis of the serine-threonine phosphatase inhibitor microcystin-LA

Author keywords

[No Author keywords available]

Indexed keywords

CYANOGINOSIN; ENZYME INHIBITOR; MICROCYSTIN LA; UNCLASSIFIED DRUG;

EID: 0029959471     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja961683e     Document Type: Article
Times cited : (83)

References (120)
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    • The distal ester of this compound is surprisingly unreactive, presumably due to steric hinderance from the N-phenylfluorenyl and α-methyl groups. The compound does not react with hydrazine in refluxing methanol. The failure of ester hydrazinolysis with hindered substrates has been noted before: Davies, J. S.; Mohammed, A. K. J. Chem. Soc., Perkin Trans. 1 1981, 2982.
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    • 1H NMR). Assuming it to result from base catalyzed epimerization competing with saponification, we attempted a number of alternative saponification methods but with no success. Cesium carbonate (ref 66a) gave levels of isomerization comparable to those observed with lithium hydroxide, and barium hydroxide gave more isomerization. Lithium hydroperoxide (ref 66b-d) generated only small amounts of the desired product along with multiple side products. The level of isomerization during this step is consistent with levels observed by Schreiber and Valentekovich for the analogous saponification step in their synthesis of motuporin: Dr. Robert J. Valentekovich, The University of California at Irvine, personal communication, 1996.
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    • note
    • 3 exhibited the presence of one major rotamer and < 10% of a minor one, which began to coalesce at 45 °C.


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