Preparations of antifungal Sch 42427/SM 9164: Preparative chromatographic resolution, and total asymmetric synthesis via enzymatic preparation of chiral α-hydroxy arylketones

Tetrahedron Letters

Volumn 37, Issue 5, 1996, Pages 611-614

  Gala, Dinesh ^a   DiBenedetto, Donald J ^a   Clark, Jon E ^a   Murphy, Bruce L ^a   Schumacher, Doris P ^a   Steinman, Martin ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; GENACONAZOLE; SCH 42427; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REACTION ANALYSIS;

EID: 0030029079     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02234-1     Document Type: Article

References (27)

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16. Since the allylic epoxidation is expected to lead to the wrong chirality at the benzylic center, the epoxide with chirality similar to 7 would entail further manipulations. No reports for the preparation of the diols similar to 8 via the dihyroxylation are known, presumably due to the difficulties in preparing the requisite trisubstituted olefins.
17. 4 and concentrated to obtain the separated isomers. Finally, each isomer was recrystallized from EtOAc/hexane to obtain 175g each of Sch 42427, and Sch 42426.
18. 3CN can be recycled on a larger scale.
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22. The ees of esters were determined with Chiracel AS®, 254nm, 7-7.5% i-PrOH/hexane, flow: 0.7-0.9 ml/min. The base line separation of the enantiomers was established by using the racemic esters.
23. The ees of alcohols were determined with Chiracel OB®, 220nm, 4-7% i-PrOH/hexane, now: 0.7-1.1 ml/min. The base line separation of the enantiomers was established by using the racemic alcohols.
24. 3 has been reported by Davis, F.A.; Haque, M. S. J. Org. Chem. 1986, 51, 4085. Our ees (verified by chiral LC), and specific rotation agree with this result.
25. (a) Milsunobu, O. Synthesis, 1981, 1;
26. (b) Hughes, D. L. Org. React., 1992, 42, 335.
27. The yields reported in this manuscript represent the product content in the worked up reactions. The small amounts of unreacied substrates and the regio isomers accounted for the rest of the mass. A detailed account will be available in a full paper.