Conformational locking through allylic strain as a device for stereocontrol - Total synthesis of grandisine A

Angewandte Chemie - International Edition

Volumn 46, Issue 41, 2007, Pages 7789-7792

  Maloney, David J ^a   Danishefsky, Samuel J ^a,b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

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

Author keywords

Allylic strain; Cycloaddition; Natural products; Steric hindrance; Total synthesis

Indexed keywords

ALLYLIC STRAINS; GRANDISINES; SILYL ENOL ETHERS; STERIC HINDRANCES;

ALDEHYDES; BINDING ENERGY; CYCLOADDITION; ETHERS; PROTONATION;

STEREOCHEMISTRY;

GRANDISINE A; INDOLIZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMISTRY; CONFORMATION; STEREOISOMERISM; SYNTHESIS;

INDOLIZINES; MOLECULAR CONFORMATION; STEREOISOMERISM;

EID: 35349026226     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200703245     Document Type: Article

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23. The relative stereochemistry was determined by extensive 2D NMR analysis; see the Supporting Information for a detailed procedure of the HPLC (chiral support) separation of the enantiomers.
24. 2, -78°C.
25. A more direct route that involved a cross-metathesis of 18 with methyl or ethyl acrylate was attempted; however, despite a number of different catalysts and reaction conditions being used, only starting material was recovered. Presumably this result is due to the hindered nature of the vinyl group.
26. 13C spectra of the authentic and synthetic natural products. The accuracy of our polarimeter was verified with commercially available optically pure compounds (R)-(+)-1,1′-bi-2-naphthol and (S)-(-)-4-benzyl-2- oxazolidinone.
27. 13C spectra of which are provided in the Supporting Information. Hence there can be no doubt that the relative configuration of synthetic 1 corresponds to that of natural grandisine A. It also seems likely (discrepancies in the magnitude of dextrarotation notwithstanding) that the absolute configuration of synthetic 1 also corresponds to that of natural grandisine A.
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