Norethindrone acetate (NA) and ethinyl estradiol (EE) related oxidative transformation products in stability samples of formulated drug product: synthesis of authentic references

被引：12

作者：

Ekhato, IV ^{[1
]}

Hurley, T ^{[1
]}

Lovdahl, M ^{[1
]}

Revitte, TJ ^{[1
]}

Guo, LY ^{[1
]}

Huang, Y ^{[1
]}

Clipper, S ^{[1
]}

Colson, C ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Dept Chem Res & Dev, Ann Arbor, MI 48105 USA

来源：

STEROIDS | 2002年 / 67卷 / 3-4期

关键词：

steroid; norethindrone acetate; ethinyl estradiol; synthesis; oxidation products;

D O I：

10.1016/S0039-128X(01)00149-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Preparative chemical methods for the synthesis of eight oxidative transformation products of ethinyl estradiol (EE) and norethindrone acetate (NA) are described. The prepared materials are useful as reference materials and standards for pharmaceutical analysis of EE and NA as bulk chemical or in formulated product. All eight products result from oxidation of the A and/or B rings of the parent compounds. Oxidation of the heteroannular 3,5 dienyl acetate derivative of NA resulted in the 6alpha-hydroxy, 6beta-hydroxy and 6-keto NA. Oxidation of 6-keto NA led to the preparation of 6alpha-hydroxy, 6beta-hydroxy, 6-keto- and Delta(6) EE. Delta(11) EE was prepared from estrone. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：165 / 174

页数：10

共 21 条

[1] THE STRUCTURE AND FUNCTION OF ESTROGENS .4. SYNTHESIS OF 17-ALPHA-ETHYNYLOESTRADIOL SPECIFICALLY POLYDEUTERATED IN RING-C [J].

COLLINS, DJ ;

SJOVALL, J .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1983, 36 (02) :339-360

[2]

COTTER ML, 1978, TETRAHEDRON LETT, V22, P1939

[3]

GARDI R, 1972, ORGANIC REACTIONS ST, P375

[4]

GASRDI R, 1967, J ORG CHEM, V32, P2647

[5] REACTION OF SOME STEROIDAL TOSYLHYDRAZONES WITH LITHIUM ALKYLS [J].

HERZ, JE ;

GONZALEZ, E ;

MANDEL, B .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1970, 23 (04) :857-&

[6] SYNTHESIS OF 1,3,5(10)-ESTRATRIEN-6-ONES [J].

HOFMEISTER, H ;

LAURENT, H ;

WIECHERT, R .

CHEMISCHE BERICHTE-RECUEIL, 1973, 106 (02) :723-726

[7] Progress in the Mitsunobu reaction. A review [J].

Hughes, DL .

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL, 1996, 28 (02) :127-164

[8] 15 beta-Hydroxysteroids .5. Steroids of the human perinatal period: The synthesis of 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one from 15 beta, 17 alpha-dihydroxy-4-pregnen-3,20-dione [J].

Joannou, GE ;

Reeder, AY .

STEROIDS, 1996, 61 (01) :18-21

[9] ON STEROIDS .367. SYNTHESIS OF RIA HAPTENS - 3-ALPHA,11-ALPHA-DIHYDROXY-5-ALPHA-PREGNAN-20-ONE 11-HEMISUCCINATE [J].

KASAL, A ;

PASZTOROVA, S .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1993, 58 (03) :619-628

[10] THE USE OF DIETHYL AZODICARBOXYLATE AND TRIPHENYLPHOSPHINE IN SYNTHESIS AND TRANSFORMATION OF NATURAL-PRODUCTS [J].

MITSUNOBU, O .

SYNTHESIS-STUTTGART, 1981, (01) :1-28

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