Formal Asymmetric Synthesis
of (-)-Aphanorphine via Ring-Closing Metathesis
Reaction

Xiaobao Yang; Bin Cheng; Zhong Li; Hongbin Zhai

doi:10.1055/s-0028-1083498

LETTER

Formal Asymmetric Synthesis of (-)-Aphanorphine via Ring-Closing Metathesis Reaction

Xiaobao Yang^a,b, Bin Cheng^b, Zhong Li*^a, Hongbin Zhai*^b
^a Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China
^b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
e-Mail: zhaih@mail.sioc.ac.cn;

Abstract

All articles of this category

Abstract

We have developed an asymmetric route to (-)-aphanorphine from O-Me-d-tyrosine methyl ester hydrochloride salt, available from d-tyrosine in four steps. The tricyclic framework of (-)-aphanorphine was assembled stereoselectively by intramolecular Friedel-Crafts reaction of the corresponding bicyclic precursor, which was in turn generated via ring-closing metathesis reaction.

Key words

aphanorphine - asymmetric synthesis - ring-closing metathesis reaction - tyrosine

Full Text

References

References and Notes

<A NAME="RU07508ST-1">1</A> Gulavita N. Hori A. Shimizu Y. Laszlo P. Clardy J. Tetrahedron Lett. 1988, 29: 4381

<A NAME="RU07508ST-2">2</A> Palmer DC. Strauss MJ. Chem. Rev. 1977, 77: 1

<A NAME="RU07508ST-3">3</A> For a recent review, see: Zezula J. Hudlicky T. Synlett 2005, 388

<A NAME="RU07508ST-4">4</A> Taylor SK. Ivanovic M. Simons LJ. Davis MM. Tetrahedron: Asymmetry 2003, 14: 743 ; and references cited therein

<A NAME="RU07508ST-5A">5a</A> Zhai H. Luo S. Ye C. Ma Y. J. Org. Chem. 2003, 68: 8268

<A NAME="RU07508ST-5B">5b</A> Hu H. Zhai H. Synlett 2003, 2129

<A NAME="RU07508ST-5C">5c</A> Ma Z. Zhai H. Synlett 2007, 161

<A NAME="RU07508ST-5D">5d</A> Ma Z. Hu H. Xiong W. Zhai H. Tetrahedron 2007, 63: 7523

<A NAME="RU07508ST-5E">5e</A> Yang X. Li Z. Zhai H. Org. Lett. 2008, 10: 2457

For synthesis of (-)-aphanorphine, see:

<A NAME="RU07508ST-6A">6a</A> Takano S. Inomata K. Sato T. Takahashi M. Ogasawara K. J. Chem. Soc., Chem. Commun. 1990, 290

<A NAME="RU07508ST-6B">6b</A> Hulme AN. Henry SS. Meyers AI. J. Org. Chem. 1995, 60: 1265

<A NAME="RU07508ST-6C">6c</A> Hallinan KO. Honda T. Tetrahedron 1995, 51: 12211

<A NAME="RU07508ST-6D">6d</A> Fadel A. Arzel P. Tetrahedron: Asymmetry 1995, 6: 893

<A NAME="RU07508ST-6E">6e</A> Meyers AI. Schmidt W. Santiago B. Heterocycles 1995, 40: 525

<A NAME="RU07508ST-6F">6f</A> Node M. Imazato H. Kurosaki R. Kawano Y. Inoue T. Nishide K. Fuji K. Heterocycles 1996, 42: 811

<A NAME="RU07508ST-6G">6g</A> Shiotani S. Okada H. Nakamata K. Yamamoto T. Sekino F. Heterocycles 1996, 43: 1031

<A NAME="RU07508ST-6H">6h</A> Shimizu M. Kamikubo T. Ogasawara K. Heterocycles 1997, 46: 21

<A NAME="RU07508ST-6I">6i</A> Fadel A. Arzel P. Tetrahedron: Asymmetry 1997, 8: 371

<A NAME="RU07508ST-6J">6j</A> Tamura O. Yanagimachi T. Kobayashi T. Ishibashi H. Org. Lett. 2001, 3: 2427

<A NAME="RU07508ST-6K">6k</A> Tanaka K. Taniguchi T. Ogasawara K. Tetrahedron Lett. 2001, 42: 1049

<A NAME="RU07508ST-6L">6l</A> ElAzab AS. Taniguchi T. Ogasawara K. Heterocycles 2002, 56: 39

<A NAME="RU07508ST-6M">6m</A> Tamura O. Yanagimachi T. Ishibashi H. Tetrahedron: Asymmetry 2003, 14: 3033

<A NAME="RU07508ST-6N">6n</A> Taylor SK. Ivanovic M. Simons LJ. Davis MM. Tetrahedron: Asymmetry 2003, 14: 743

<A NAME="RU07508ST-6O">6o</A> Kita Y. Futamura J. Ohba Y. Sawama Y. Ganesh JK. Fujioka H. J. Org. Chem. 2003, 68: 5917

<A NAME="RU07508ST-6P">6p</A> Bower JF. Szeto P. Gallagher T. Chem. Commun. 2005, 5793

<A NAME="RU07508ST-6Q">6q</A> Katoh M. Inoue H. Suzuki A. Honda T. Synlett 2005, 2820

<A NAME="RU07508ST-6R">6r</A> Li M. Zhou P. Roth HF. Synthesis 2007, 55

<A NAME="RU07508ST-6S">6s</A> Bower JF. Szeto P. Gallagher T. Org. Biomol. Chem. 2007, 5: 143

<A NAME="RU07508ST-6T">6t</A> Grainger RS. Welsh EJ. Angew. Chem. Int. Ed. 2007, 46: 5377

For the synthesis of (±)-aphanorphine, see:

<A NAME="RU07508ST-6U">6u</A> Honda T. Yamamoto A. Cui Y. Tsubuki M. J. Chem. Soc., Perkin Trans. 1 1992, 531

<A NAME="RU07508ST-6V">6v</A> Fuchs JR. Funk RL. Org. Lett. 2001, 3: 3923

For the synthesis of (+)-aphanorphine, see:

<A NAME="RU07508ST-6W">6w</A> Takano S. Inomata K. Sato T. Ogasawara K. J. Chem. Soc., Chem. Commun. 1989, 1591

<A NAME="RU07508ST-7">7</A> For the synthesis of O-Me-d-tyrosine methyl ester hydrochloride salt(4), see: Hulme AN. Rosser EM. Org. Lett. 2002, 4: 265

<A NAME="RU07508ST-8">8</A> For Swern oxidation, see: Anthory JM. Debra SB. Daniel S. J. Org. Chem. 1979, 44: 4148

<A NAME="RU07508ST-9">9</A> Scholl M. Ding S. Lee CW. Grubbs RH. Org. Lett. 1999, 1: 953

Compound 8: white solid; mp 136-138 ˚C (Lit.^5a 137-138 ˚C); [α]_D ^²5 -16.9 (c 0.89, CHCl₃) {Lit.^5a [α]_D ^²0 -13.4 (c 0.97, CHCl₃); Lit.^5b [α]_D ^²0 -14.3 (c 0.93, CHCl₃)}. ^¹H NMR (300 MHz, CDCl₃): δ = 1.41 (s, 3 H), 1.41-1.49 (m, 1 H), 1.79 (d, J = 11.1 Hz, 1 H), 2.43 (s, 3 H), 2.91-3.16 (m, 2 H), 3.03 (d, J = 8.4 Hz, 1 H), 3.41 (d, J = 8.7 Hz, 1 H), 3.80 (s, 3 H), 4.40 (t, J = 3.3 Hz, 1 H), 6.74 (dd, J = 8.4, 2.4 Hz, 1 H), 6.79 (d, J = 2.7 Hz, 1 H), 6.99 (d, J = 8.1 Hz, 1 H), 7.30 (d, J = 8.1 Hz, 2 H), 7.71 (d, J = 8.1 Hz, 2 H). ^¹³C NMR (75.47 MHz, CDCl₃): δ = 20.8, 21.6, 38.3, 41.8, 42.4, 55.4, 58.0, 63.1, 110.3, 111.9, 125.5, 127.3, 129.8, 130.6, 135.9, 143.4, 145.1, 158.2. ESI-MS: m/z = 380 [M + Na], 358 [M + H]. ESI-HRMS: m/z calcd for C₂₀H₂₃NO₃S + H: 358.1477; found: 358.1473. ESI-HRMS: m/z calcd for C₂₂H₂₃NO₃S + Na: 380.1296; found: 380.1308.