A short and efficient synthesis of L-5,5,5,5',5',5'-hexafluoroleucine from N-Cbz-L-serine

被引：42

作者：

Anderson, JT

Toogood, PL

Marsh, ENG ^{[1
]}

机构：

[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

[2] Pfizer Global Res & Dev, Ann Arbor Labs, Ann Arbor, MI 48105 USA

来源：

ORGANIC LETTERS | 2002年 / 4卷 / 24期

关键词：

D O I：

10.1021/ol026922j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] 5,5,5,5',5',5'-Hexafluoroleucine (6), a fluorous analogue of leucine, is of considerable interest as a building block in the design of fluorous proteins and peptides. We report a short and efficient synthesis of 6, which is obtained from N-Cbz-L-serine (1) in 50% overall yield, 99% enantiomeric excess, and In multigram quantities. Key steps are addition of a serine-derived organozincate to hexafluoroacetone to construct the hexafluoroleucine side chain, followed by radical-mediated deoxygenation of the resulting tertiary alcohol.

引用

收藏

页码：4281 / 4283

页数：3

相关论文

共 24 条

[1] POTASSIUM FLUORIDE ON CELITE - VERSATILE REAGENT FOR C-ALKYLATION,N-ALKYLATION,O-ALKYLATION, AND S-ALKYLATION [J].

ANDO, T ;

YAMAWAKI, J .

CHEMISTRY LETTERS, 1979, (01) :45-46

[2] Programmed self-sorting of coiled coils with leucine and hexafluoroleucine cores [J].

Bilgiçer, B ;

Xing, X ;

Kumar, K .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (47) :11815-11816

[3] A coiled coil with a fluorous core [J].

Bilgiçer, B ;

Fichera, A ;

Kumar, K .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (19) :4393-4399

[4] FACILE SYNTHESIS OF TERT-BUTYL ESTER OF N-PROTECTED AMINO-ACIDS WITH TERT-BUTYL BROMIDE [J].

CHEVALLET, P ;

GARROUSTE, P ;

MALAWSKA, B ;

MARTINEZ, J .

TETRAHEDRON LETTERS, 1993, 34 (46) :7409-7412

[5] ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES [J].

DALE, JA ;

DULL, DL ;

MOSHER, HS .

JOURNAL OF ORGANIC CHEMISTRY, 1969, 34 (09) :2543-&

[6] A new route to hydrophobic amino acids using copper-promoted reactions of serine-derived organozinc reagents [J].

Deboves, HJC ;

Grabowska, U ;

Rizzo, A ;

Jackson, RFW .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 2000, (24) :4284-4292

[7] A NEW METHOD FOR THE DEOXYGENATION OF TERTIARY AND SECONDARY ALCOHOLS [J].

DOLAN, SC ;

MACMILLAN, J .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1985, (22) :1588-1589

[8] Synthesis of macrocyclic, potential protease inhibitors using a generic scaffold [J].

Dumez, E ;

Snaith, JS ;

Jackson, RFW ;

McElroy, AB ;

Overington, J ;

Wythes, MJ ;

Withka, JM ;

McLellan, TJ .

JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (14) :4882-4892

[9] Stereoselective synthesis of all stereoisomeric 2-amino-3-hydroxy-4-phenylbutanolides [J].

Gair, S ;

Jackson, RFW ;

Brown, PA .

TETRAHEDRON LETTERS, 1997, 38 (17) :3059-3062

[10] FACILE CATALYST SEPARATION WITHOUT WATER - FLUOROUS BIPHASE HYDROFORMYLATION OF OLEFINS [J].

HORVATH, IT ;

RABAI, J .

SCIENCE, 1994, 266 (5182) :72-75