Total synthesis of enantiopure phalarine via a stereospecific pictet-spengler reaction: Traceless transfer of chirality from L -tryptophan

Journal of the American Chemical Society

Volumn 132, Issue 24, 2010, Pages 8506-8512

  Trzupek, John D ^a   Lee, Dongjoo ^a   Crowley, Brendan M ^a   Marathias, Vasilios M ^b   Danishefsky, Samuel J ^a,c  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b PFIZER INC   (United States)

^c Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIASTEREOSELECTIVE; ENANTIOPURE; L-TRYPTOPHAN; NATURALLY OCCURRING; PICTET-SPENGLER REACTIONS; SINGLE-STEP; STEREOSPECIFIC; TOTAL SYNTHESIS;

AMINO ACIDS; STEREOCHEMISTRY;

SYNTHESIS (CHEMICAL);

ALKALOID; PHALARINE; TRYPTAMINE; TRYPTOPHAN; UNCLASSIFIED DRUG;

AMINO ACID ANALYSIS; AMINO ACID SUBSTITUTION; AMINO ACID SYNTHESIS; ARTICLE; CHIRALITY; CYCLIZATION; DECARBOXYLATION; ENANTIOMER; ENANTIOSELECTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; PICTET SPENGLER REACTION; PROTEIN STRUCTURE; STEREOCHEMISTRY; STEREOSPECIFICITY; STRUCTURE ANALYSIS;

ALKALOIDS; STEREOISOMERISM; SUBSTRATE SPECIFICITY; TRYPTOPHAN;

EID: 77953648519     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja1030968     Document Type: Article

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41. As was the case with compound 29, the formation of 41 was completely reversible. Upon resubjection to the reaction conditions for formation of 41 without dessicant, 39 was cleanly recovered without any loss in optical purity (data not shown).
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47. Attempts to evaluate the reversibility of the late steps in the synthesis were undertaken. The thought was to subject the final optically pure phalarine to treatment with CSA in order to determine whether it would undergo racemization. However, in the event, this type of treatment resulted in major decomposition of phalarine, no doubt resulting from the instability of gramine side chains toward acidic agents.