(2S,3R)-3-하이드록시호모세린락톤의 입체선택적 합성 : 바이닐글라이신 OBO Ester 유도체의 입체선택적인 이중알콜화 반응

고무현; 전종호; 김영규; Moo-hyun Koh; Jongho Jeon; Young Gyu Kim

Applied Chemistry for Engineering, Vol.31, No.2, 187-192, April, 2020

DOI10.14478/ace.2020.1019 Export Citation

(2S,3R)-3-하이드록시호모세린락톤의 입체선택적 합성 : 바이닐글라이신 OBO Ester 유도체의 입체선택적인 이중알콜화 반응

Stereoselective Synthesis of (2S,3R)-3-Hydroxyhomoserine Lactone via anti Selective Dihydroxylation of an OBO Group-Protected Vinyl Glycine Analog

고무현, 전종호^{1, †}, 김영규^†

서울대학교 공과대학 화학생물공학부
¹경북대학교 공과대학 응용화학공학부 응용화학전공

Moo-hyun Koh, Jongho Jeon^{1, †}, and Young Gyu Kim^†

School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
¹Department of Applied Chemistry, School of Applied Chemical Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea

E-mail:,

초록

(2S,3R)-3-hydroxyhomoserine lactone (HSL)은 생리학적 활성을 가지는 다양한 종류의 화합물을 합성하기 위한 중간체로 활용되어 왔다. 본 논문에서는 OBO ester로 보호된 바이닐글라이신 유도체에 이중알콜화 반응을 수행하여 효율적인 HSL 합성 결과를 보고하고자 한다. 바이닐글라이신의 비고리 conformation은 크기가 큰 OBO ester에 의해 조절되었으며 N-inside conformation을 통해 이중알콜화 반응이 진행됨으로써 높은 anti 선택성(> 10 : 1)을 얻을 수 있었다. 이러한 결과를 바탕으로 N-Cbz-L-serine을 출발물질로 사용하여 총 7단계 34%의 수율로 HSL을 합성할 수 있었다. 본 연구의 결과는 amino diol 구조를 가지는 다양한 생리활성 천연물들의 입체선택적인 합성에 유용하게 활용될 수 있을 것으로 기대된다.

(2S,3R)-3-hydroxyhomoserine lactone (HSL) has been used as a key intermediate for the synthesis of various biologically active compounds. In this study, we demonstrated an efficient synthesis of HSL via anti selective dihydroxylation of a protected vinyl glycine analog with an oxabicyclo[2.2.2]octyl orthoester (OBO) ester group. Because the acyclic conformation of the substrate was efficiently controlled by the bulky OBO ester group, a diastereoselectivity of > 10 : 1 was obtained in the dihydroxylation reaction without the use of a chiral reagent. By using this result, the target compound 1 can be obtained from commercially available N-Cbz-L-serine 2 in seven steps with an overall yeid of 34%. This result could be applied to the stereoselective synthesis of biologically active molecules containing a vicinal amino diol moiety.

Keywords:(2S,3R)-3-Hydroxyhomoserine lactone;Dihydroxylation;Vinyl glycine analog;Stereoselective synthesis;OBO ester

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[1] Ye CX, Melcamu YY, Li HH, Cheng JT, Zhang TT, Ruan YP, Zheng X, Lu X, Huang PQ, Nat. Commun., 9, 410 (2018)

[2] Heravi MM, Lashaki TB, Fattahi B, Zadsirjan V, RSC Adv., 8, 6634 (2018)

[3] Karjalainen OK, Koskinen AMP, Org. Biomol. Chem., 10, 4311 (2012)

[4] Jeon J, Shin N, Kim YG, Appl. Chem. Eng., 25, 437 (2014)

[5] Oh JS, Park DY, Song BS, Bae JG, Yoon SW, Kim YG, Tetrahedron Lett., 43, 7209 (2002)

[6] Oh JS, Jeon J, Park DY, Kim YG, Chem. Commun., 41, 770 (2005)

[7] Jeon J, Hong SK, Oh JS, Kim YG, J. Org. Chem., 71, 3310 (2006)

[8] Jeon J, Lee JH, Kim JW, Kim YG, Tetrahedron: Asymmetry, 18, 2448 (2007)

[9] Jeon J, Shin N, Lee JH, Kim YG, Appl. Chem. Eng., 25(4), 392 (2014)

[10] Jeon J, Shin M, Yoo JW, Oh JS, Bae jG, Jung SH, Kim YG, Tetrahedron Lett., 48, 1105 (2007)

[11] Jeon J, Kim SH, Lee JH, Kim YG, Bull. Korean Chem. Soc., 30, 1003 (2009)

[12] Blaskovich MA, Lajoie GA, J. Am. Chem. Soc., 115, 5021 (1993)

[13] Blaskovich MA, Evindar G, Rose NGW, Wilkinson s, Luo Y, Lajoie GA, J. Org. Chem., 63, 3631 (1998)

[14] Hansen DB, Wan X, Carroll PJ, Joullie MM, J. Org. Chem., 70, 3120 (2005)

[15] houk KN, Duh HY, Wu YD, Moses SR, J. Am. Chem. Soc., 108, 2754 (1986)

[16] Koh M, Ph. D. Dissertation, Seoul National University, Seoul, Republic of Korea (2009).

[17] Pirrung MC, Nunn DS, McPhail AT, Bioorg. Med. Chem. Lett., 3, 2095 (1993)

[18] Olsen JA, Severinsen R, Ramussen TB, Hentzer M, Givskov M, Nielsen J, Bioorg. Med. Chem. Lett., 12, 325 (2002)

[19] Ikunaka M, Matsumoto J, Fujima Y, Hirayama Y, Org. Process Res. Dev., 6, 49 (2002)

[20] Vassilev VP, Uchiyama T, Kajimoto T, Wong CH, Tetrahedron Lett., 28, 5063 (1995)