Convenient Synthesis of 3-(S)-Amino-γ-butyrolactone

Martha Sibrian-Vazquez; David A. Spivak

doi:10.1055/s-2002-32597

LETTER

Convenient Synthesis of 3-(S)-Amino-γ-butyrolactone

Martha Sibrian-Vazquez, David A. Spivak*
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Fax: +1(225)5783458; e-Mail: David_Spivak@chem.lsu.edu;

Abstract

All articles of this category

Abstract

An efficient two step conversion of N-t-Boc-l-aspartic acid β-benzyl ester to enantiopure 3-(S)-amino-γ-butyrolactone is described. In this route, chemoselective reduction of the α-carboxylic group in the starting material via a mixed anhydride with NaBH₄ afforded the corresponding alcohol in 95% yield without any loss of the optical purity. Subsequent acidic hydrolysis of the N-protected β-amino alcohol not only deprotected the amino group, but also produced the desired γ-lactone in 98% yield with complete retention of the optical activity.

Key words

amino acids - amino alcohols - lactones - reductions - ring closure

Full Text

References

<A NAME="RS00502ST-1A">1a</A> Bovy PR, Rico JG, and Rogers TE. inventors; U.S. Patent 6 037 365. ; Chem. Abstr. 2000, 132, 207753

<A NAME="RS00502ST-1B">1b</A> Bovy PR, Rico JG, and Rogers TE. inventors; U.S. Patent 9 506 038. ; Chem. Abstr. 1995, 123, 33068

<A NAME="RS00502ST-1C">1c</A> Bovy PR, Rico JG, and Rogers TE. inventors; U.S. Patent 9 312 103. ; Chem. Abstr. 1993, 120, 106764

<A NAME="RS00502ST-2A">2a</A> Askew BC, Hartman GD, Duggan ME, Young SD, Hutchinson JH, Wai JS, Egbertson MS, Vassallo LM, Libby LA, Ihle NC, Krause AE, and Halczenko W. inventors; U.S. Patent 9 714 417. ; Chem. Abstr. 1997, 126, 5353

<A NAME="RS00502ST-2B">2b</A> Askew BC, Hartman GD, Duggan ME, Young SD, Hutchinson JH, Wai JS, Egbertson MS, Vassallo LM, Libby LA, Ihle NC, Krause AE, and Halczenko W. inventors; U.S. Patent 5 852 045. ; Chem. Abstr. 1998, 130, 66809

<A NAME="RS00502ST-2C">2c</A> Sato M, Mannaka A, Takahashi K, Kawashima Y, and Hatayama K. inventors; J. P. Patent 7 206 860. ; Chem. Abstr. 1995, 124, 8804

<A NAME="RS00502ST-2D">2d</A> Hartman GD, Prugh JD, Halczenko W, Egbertson M, and Ihle N. inventors; U.S. Patent 9 504 531. ; Chem. Abstr. 1995, 123, 228162

<A NAME="RS00502ST-3">3</A> Ruminski PG, Clare M, Collins PW, Desai BN, Lindmark RJ, Rico JG, Rogers TE, and Russell MA. inventors; U.S. Patent 9 708 145. ; Chem. Abstr. 1997, 126, 264011

<A NAME="RS00502ST-4">4</A> Mullican MD. Lauffer DJ. Gillispie RJ. Matharu SS. Kay D. Porrit GM. Evans PL. Golec JMC. Murcko MA. Bioorg. Med. Chem. Lett. 1994, 4(19): 2359

<A NAME="RS00502ST-5A">5a</A> Chu DT, and Li Q. inventors; U.S. Patent 5 252 747. ; Chem. Abstr. 1993, 120, 298642

<A NAME="RS00502ST-5B">5b</A> Ashina Y, Fukuda Y, and Fukuda H. inventors; E. P. Patent 443 498. ; Chem. Abstr. 1991, 115, 256018

<A NAME="RS00502ST-6">6</A> Nagai K. Tanaka R. Murakami H. Sano A. Arzneim-Forsch. 1967, 17: 1575 ; Chem. Abstr. 1967, 68, 67444

<A NAME="RS00502ST-7">7</A> McGarvey GJ. Williams JM. Hiner RN. Matsubara Y. Oh T. J. Am. Chem. Soc. 1986, 108: 4943

<A NAME="RS00502ST-8">8</A> Rinehart KL. Harada K. Namikoshi M. Chen C. Harvis CA. Munro MHG. Blunt JW. Mulligan PE. Beasley VR. Dahlem AM. Carmichel WW. J. Am. Chem. Soc. 1988, 110: 8557

<A NAME="RS00502ST-9">9</A> Atmani A. El Hallaoui A. El Hajji S. Roumestant ML. Viallefont P. Synth. Commun. 1971, 21: 2383

<A NAME="RS00502ST-10">10</A> Hvidt T. Szarek WA. Maclean DB. Can. J. Chem. 1988, 66: 779

<A NAME="RS00502ST-11">11</A> Calvisi G. Catini R. Chiariotti W. Giannessi F. Muck S. Tinti MO. De Angelis F. Synlett 1997, 71

Benzyl (3 S )-[( tert -butoxycarbonyl)amino]-4-hydroxy-butanoate(3). Prepared from N-t-boc-l-aspartic acid
β-benzyl ester following a literature procedure [13d] as a white solid. Yield 95%, ee > 98%. Enantiomeric excess was determined by HPLC using a normal phase Chiralpak AD column, hexanes-isopropanol 90:10, 1 mL/min, at 250 nm, mp 62-63.8 °C [α]_D ²⁵ -6.0 (c = 1, MeOH); lit. [13e] [α]_D -6.0 (c = 1, MeOH). ¹H NMR (250 MHz; CDCl₃), δ: 7.33 (s, 5 H), 5.28 (s, 1 H), 5.11 (s, 2 H), 4.00 (s, 1 H), 3.64 (d, J = 4.7 Hz, 2 H), 2.88 (s, 1 H), 2.64 (d, J = 6.2 Hz, 2 H), 1.42 (s, 9 H). ¹³C NMR (67.5 MHz; CDCl₃) δ: 172.06, 156.23, 135.99, 129.02, 128.76, 128.66, 107.82, 80.29, 67.05, 49.87, 36.47, 28.76. MS (FAB) (M + H⁺) calcd 310.16, found 310.10. Anal. Calcd. for C₁₆H₂₃NO₅: C, 62.12; H, 7.49; N, 4.53. Found C, 61.72; H, 7.39; N, 4.41.

<A NAME="RS00502ST-13A">13a</A> Seki H. Koga K. Matsu H. Ohki S. Matsuo I. Yamada S. Chem. Pharm. Bull. 1965, 13: 995

<A NAME="RS00502ST-13B">13b</A> Soai K. Bull. Chem. Soc. Jpn. 1984, 57: 2327

<A NAME="RS00502ST-13C">13c</A> Soai K. Yokoyama S. Mochida K. Synthesis 1987, 647

<A NAME="RS00502ST-13D">13d</A> Kokotos G. Synthesis 1990, 299

<A NAME="RS00502ST-13E">13e</A> Rodriguez M. Linares M. Doulut S. Heitz A. Martinez J. Tetrahedron Lett. 1991, 32: 923

3-( S )-amino-γ-butyrolactone hydrochloride(1) The amino alcohol 4 (1.26g, 4 mmol) was treated with 40 mL of 2 M HCl in diethyl ether. The temperature was kept at 0 °C for 6 h, then allowed to rise to room temperature, and stirred for 18 hours. The excess of HCl and ether were evaporated first under a stream of N₂ and then under vacuum. The residue, a white solid was filtered out, washed with ethyl ether (3 × 20 mL), and dried at room temperature. Yield 98%. mp 182-184 °C. [α]_D ²⁵ -59.3 (c = 1, H₂O); lit. [11] [α]_D ²⁰ + 56.7 (c = 1, H₂O) (R) form. ¹H NMR [250 MHz; (DMSO-d₆)] δ: 8.76 (s, 3 H), 4.5 (dd, J = 10.4 Hz, J = 6.6 Hz, 1 H), 4.36 (dd, J = 10.4 Hz, J = 2.7 Hz, 1 H), 4.10 (m, 1 H), 3.0 (dd, J = 18.3, J = 8.5 Hz, 1 H), 2.57 (dd, J = 18.3 Hz, J = 2.9 Hz, 1 H). ¹³C NMR: [67.5 MHz; (DMSO-d₆)] δ: 175.39, 71.05, 41.19, 33.42. MS (FAB) (M + H⁺) calcd. 102.1, found 102.1. Anal. Calcd. for C₄H₈ClNO₂: C, 34.92; H, 5.86; N, 10.18; Cl, 25.77. Found C, 34.99; H, 5.62; N, 10.08; Cl, 25.12.