An efficient chiral moderator prepared from inexpensive (+)3-carene: Synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963

被引：184

作者：

Kauffman, GS ^{[1
]}

Harris, GD ^{[1
]}

Dorow, RL ^{[1
]}

Stone, BRP ^{[1
]}

Parsons, RL ^{[1
]}

Pesti, JA ^{[1
]}

Magnus, NA ^{[1
]}

Fortunak, JM ^{[1
]}

Confalone, PN ^{[1
]}

Nugent, WA ^{[1
]}

机构：

[1] Dupont Merck Pharmaceut Co, Chem Proc R&D, Chambers Works, Deepwater, NJ 08023 USA

来源：

ORGANIC LETTERS | 2000年 / 2卷 / 20期

关键词：

D O I：

10.1021/ol006321x

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.

引用

页码：3119 / 3121

页数：3

共 21 条

[1] HYDROBORATION OF TERPENES .4. HYDROBORATION OF (+)-3-CARENE (DELTA3-CARENE) . CONFIGURATION ASSIGNMENTS FOR 4-CARANOLS AND 4-CARARONES . AN UNUSUAL STABILITY OF 4-ISOCARANONE WITH A CIS RELATIONSHIP OF METHYL AND GEM-DIMETHYL GROUPS [J].

BROWN, HC ;

SUZUKI, A .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1967, 89 (08) :1933-&

[2] Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1 [J].

Corbett, JW ;

Ko, SS ;

Rodgers, JD ;

Jeffrey, S ;

Bacheler, LT ;

Klabe, RM ;

Diamond, S ;

Lai, CM ;

Rabel, SR ;

Saye, JA ;

Adams, SP ;

Trainor, GL ;

Anderson, PS ;

Erickson-Viitanen, SK .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (12) :2893-2897

[3]

Fedyunina I. V., 1992, CHEM NAT COMPD, V28, P173

[4]

Gianini M, 1996, SYNTHESIS-STUTTGART, P702

[5] THE REARRANGEMENT OF ALIPHATIC ETHYLENE OXIDES [J].

HOUSE, HO .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1955, 77 (19) :5083-5089

[6] LITHIUM ALKOXIDES OF CINCHONA ALKALOIDS AS CHIRAL CONTROLLERS FOR ENANTIOSELECTIVE ACETYLIDE ADDITION TO CYCLIC N-ACYL KETIMINES [J].

HUFFMAN, MA ;

YASUDA, N ;

DECAMP, AE ;

GRABOWSKI, EJJ .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (06) :1590-1594

[7] Catalytic enantioselective addition to imines [J].

Kobayashi, S ;

Ishitani, H .

CHEMICAL REVIEWS, 1999, 99 (05) :1069-1094

[8] A new asymmetric 1,4-addition method: application to the synthesis of the HIV non-nucleoside reverse transcriptase inhibitor DPC 961 [J].

Magnus, NA ;

Confalone, PN ;

Storace, L .

TETRAHEDRON LETTERS, 2000, 41 (17) :3015-3019

[9] DERIVATIVES OF ( + ) -LIMONENE .3. STEREOSPECIFIC SYNTHESIS OF CIS- + TRANS-DELTA8 ) 9 ) -P-MENTHENE 1,2-EPOXIDES [J].

NEWHALL, WF .

JOURNAL OF ORGANIC CHEMISTRY, 1964, 29 (01) :185-&

[10] Homogeneous catalysis as a tool for organic synthesis [J].

Nugent, WA ;

Licini, G ;

Bonchio, M ;

Bortolini, O ;

Finn, MG ;

McCleland, BW .

PURE AND APPLIED CHEMISTRY, 1998, 70 (05) :1041-1046

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