Progress toward the Total Synthesis of Ingenol: Construction of the Complete Carbocyclic Skeleton

Organic Letters

Volumn 3, Issue 10, 2001, Pages 1563-1566

  Tang, Haifeng ^a   Yusuff, Naeem ^a   Wood, John L ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTINEOPLASTIC AGENT; DITERPENE; INGENOL; IRRITANT AGENT;

ARTICLE; SYNTHESIS;

ANTI-HIV AGENTS; ANTINEOPLASTIC AGENTS; DITERPENES; IRRITANTS;

EID: 0035902262     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol015855a     Document Type: Article

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27. A conformational search of precursor 3 illustrated that the two internal olefinic carbons are oriented 4.2 Å away from each other. With the installation of the A ring, the C ring conformation was dramatically twisted at quaternary center C(8), imparting a dihedral angle between C(8)-C(7) and C(10)-C(4) of 79.9°. Furthermore, the distance between the two internal olefinic carbons was reduced to 3.8 Å. (matrix presented)
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30. β-keto ester 16 is actually isolated from a mixture of four diastereomers produced using the literature procedure (See ref 7a). However, it was subsequently discovered that the corresponding ketals were more readily separated. Thus, the diastereomeric mixture was carried forward on a preparative scale.
31. The ketals were separated by silica gel chromatography. Four diastereomeric ketals were eluted in the ratio of 43:23:18:16. Only the major diastereomer 17 was advanced.
32. The stereochemistry of 17 was unambiguously determined by X-ray crystallography.
33. Ozonolysis of the major diastereomer 20a gave rise to a crystalline compound 21, the structure of which was established by X-ray crystallography. For spectral data pertaining to 20b and 20c, see Supporting Information. (matrix presented)