Exploring symmetry-based logic for a synthesis of Palau'amine

Journal of Organic Chemistry

Volumn 74, Issue 16, 2009, Pages 5909-5919

  Li, Qingyi ^b,c   Hurley, Paul ^a,b,d   Ding, Hui ^a   Roberts, Andrew G ^a   Akella, Radha ^b   Harran, Patrick G ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c CUBIST PHARMACEUTICALS INC   (United States)

^d Gilead Alberta ULC   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMINES; SYNTHESIS (CHEMICAL);

ALKYLIDENES; CHEMICAL EQUATIONS; DESYM-METRIZATION; NATURAL PRODUCTS; SYNTHETIC APPROACH; TOTAL SYNTHESIS;

ORGANIC COMPOUNDS;

AMINE; CYCLOPENTANE DERIVATIVE; NATURAL PRODUCT; ALKALOID; GUANIDINE DERIVATIVE; PALAU'AMINE; SPIRO COMPOUND;

ARTICLE; CHEMICAL REACTION; HALOGENATION; OXIDATION; STRUCTURE ANALYSIS; SYNTHESIS; CHEMISTRY; CYCLIZATION; DIMERIZATION; ENZYME SPECIFICITY; REPRODUCIBILITY; STEREOISOMERISM;

ALKALOIDS; CYCLIZATION; DIMERIZATION; GUANIDINES; REPRODUCIBILITY OF RESULTS; SPIRO COMPOUNDS; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

EID: 70349088599     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo900755r     Document Type: Article

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63. 2) to diastereomers 40 can also be accomplished using Zn dust in refluxing AcOH/THF. This provides 40 (40% yield) along with mono reduced material (20% yield, analogous to 27) after 30 min in the presence of 4 equiv of Zn. Extended reaction times or a larger excess of Zn leads to partial debromination.
64. In future iterations of the route (see ref 41), one path forward could entail transforming a structure of type 44 into an aminoimidazole of type 50. Installation of the dipyrrolopyrazinone motif required to complete palau'amine would then parallel Büchi's phakellin synthesis (ref 40). Presuming that process would involve 51 as an intermediate, an equilibrium established with 52 (analogous to the species thought generated from 43 en route to 44) prior to C10-N2 bond formation would render mute C16 stereochemistry in 44. We look forward to exploring these issues in detail. (Chemical Equation Presented)
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