Practical chemoenzymatic synthesis of a 3-pyridylethanolamino β3 adrenergic receptor agonist

被引：24

作者：

Chung, JYL

Ho, GJ

Chartrain, M

Roberge, C

Zhao, DL

Leazer, J

Farr, R

Robbins, M

Emerson, K

Mathre, DJ

McNamara, JM

Hughes, DL

Grabowski, EJJ

Reider, PJ

机构：

[1] Merck & Co Inc, Merck Res Labs, Dept Proc Res, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Merck Res Labs, Dept Bioproc R&D, Rahway, NJ 07065 USA

来源：

TETRAHEDRON LETTERS | 1999年 / 40卷 / 37期

关键词：

D O I：

10.1016/S0040-4039(99)01353-2

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A chemoenzymatic synthesis of beta(3) agonist 1 suitable for large scale preparation is described. The key chiral 3-pyridylethanolamine intermediate (R)-7 was prepared via an improved Neber rearrangement and a yeast-mediated asymmetric reduction. The tetrazolone fragment of the molecule was constructed via a dipolar cycloaddition between 1-(cyclopentyl)-3-propylazide and p-chlorosulfonyl phenylisocyanate. Sulfonamide coupling of these two intermediates under Shotten-Baumann conditions, followed by a borane reduction of the amide afforded 1 in 20-32% overall yield from 3-acetylpyridine, (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：6739 / 6743

页数：5

共 13 条

[1]

Arch JRS, 1996, INT J OBESITY, V20, P191

[2]

CHARTRAIN M, 1998, Patent No. 9803672

[3]

CHARTRAIN M, 1999, IN PRESS ENZYME MICR

[4]

CHARTRAIN MM, 1998, Patent No. 5792871

[5]

Fisher M H, 1996, US Patent, Patent No. 5705515

[6]

FISHER MH, 1998, Patent No. 5714506

[7] BAKERS-YEAST REDUCTION OF ALPHA-(ACYLAMINO)ACETOPHENONES AND LIPASE-CATALYZED RESOLUTION OF 2-ACYLAMINO-1-ARYLETHANOLS [J].

IZUMI, T ;

FUKAYA, K .

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1993, 66 (04) :1216-1221

[8]

La Mattina JL, 1985, ORG SYNTH, V64, P19

[9] 3-pyridylethanolamines:: Potent and selective human β3 adrenergic receptor agonists [J].

Naylor, EM ;

Colandrea, VJ ;

Candelore, MR ;

Cascieri, MA ;

Colwell, LF ;

Deng, LP ;

Feeney, WP ;

Forrest, MJ ;

Hom, GJ ;

MacIntyre, DE ;

Strader, CD ;

Tota, L ;

Wang, PR ;

Wyvratt, MJ ;

Fisher, MH ;

Weber, AE .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (21) :3087-3092

[10] L-770,644:: A potent and selective human β3 adrenergic receptor agonist with improved oral bioavailability [J].

Shih, TL ;

Candelore, MR ;

Cascieri, MA ;

Chiu, SHL ;

Colwell, LF ;

Deng, LP ;

Feeney, WP ;

Forrest, MJ ;

Hom, GJ ;

MacIntyre, DE ;

Miller, RR ;

Stearns, RA ;

Strader, CD ;

Tota, L ;

Wyvratt, MJ ;

Fisher, MH ;

Weber, AE .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (09) :1251-1254

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