Abstract
Two natural products, synerazol and pseurotin E, were synthesized from the natural product pseurotin A in 58% and 57% yields, respectively in one-pot procedures. This work also establishes the absolute stereochemistry of pseurotin E.
Article PDF
References
Bloch P, Tamm C, Bollinger P, Petcher TJ, Weber HP . Pseurotin, a new metabolite of Pseudeurotium ovalis Stolk having an unusual hetero-spirocyclic system. Helv Chim Acta 59: 133–137 ( 1976)
Komagata D, Fujita S, Yamashita N, Saito S, Morino T . Novel neuritogenic activities of pseurotin A and penicillic acid. J Antibiot 49: 958–959 ( 1996)
Wenke J, Anke H, Sterner O . Pseurotin A and 8-O-demethylpseurotin A from Aspergillus fumigatus and their inhibitory activities on chitin synthase. Biosci Biotech Biochem 57: 961–964 ( 1993)
Maebayashi Y, Horie Y, Satoh Y, Yamazaki M . Isolation of pseurotin A and a new pyrazine from Pseudallesscheria boydii. Mycotoxins 22: 33–34 ( 1985)
Wink J, Grabley S, Gareis M, Zeeck A, Phillips S . Biologically active pseurotin A and D, new metabolites from Aspergillus fumigatus, process for their preparation and their use as apomorphine antagonists. Eur Pat Appl EP546475, ( 1993)
Weber HP, Petcher TJ, Bloch P, Tamm C . The crystal and molecular structure of 12,13-dibromopseurotin. Helv Chim Acta 59: 137–140 ( 1976)
Wink J, Grabley S, Gareis M, Thiericke R, Kirsch R . Pseurotin F1/F2, new metabolites from Aspergillus fumigatus, process for their preparation and their use as apomorphine antagonists. Eur Pat Appl EP546474, ( 1993)
(a) Igarashi Y, Yabuta Y, Sekine A, Fujii K, Harada K, Oikawa T, Sato M, Furumai T, Oki T . Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin. J Antibiot 57: 748–754 ( 2004)
(b) Ando O, Satake H, Nakajina M, Sato A, Nakamura T, Kinoshita T, Furuya K, Haneishi T . Synerazol, a new antifungal antibiotic. J Antibiot 44: 382–389 ( 1991)
Asami Y, Kakeya H, Onose R, Yoshida A, Matsuzaki H, Osada H . Azaspirene: a novel angiogenesis inhibitor containing a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton produced by the fungus Neosartorya sp. Org Lett 4: 2845–2848 ( 2002)
Breitenstein W, Chexal KK, Mohr P, Tamm C . Pseurotin B, C, D, and E. Further new metabolites of Pseudeurotium ovalis STOLK. Helv Chim Acta 64: 379–388 ( 1981)
Hayashi Y, Shoji M, Yamaguchi S, Mukaiyama T, Yamaguchi J, Kakeya H, Osada H . Asymmetric total synthesis of pseurotin A. Org Lett 5: 2287–2290 ( 2003)
(a) Aoki S, Oi T, Shimizu K, Shiraki R, Takao K, Tadano K . Total syntheses of natural pseurotins A and F2 and azaspirene. Heterocycles 62: 161–166 ( 2004)
(b) Aoki S, Oi T, Shimizu K, Shiraki R, Takao K, Tadano K . Total syntheses of natural pseurotins A, F2, and azaspirene. Bull Chem Soc Jpn 77: 1703–1716 ( 2004)
Hayashi Y, Shoji M, Mukaiyama T, Gotoh H, Yamaguchi S, Nakata M, Kakeya H, Osada H . First asymmetric total synthesis of synerazol, an antifungal antibiotic, and determination of its absolute stereochemistry. J Org Chem 70: 5643–5654 ( 2005)
Hayashi Y, Shoji M, Yamaguchi J, Sato K, Yamaguchi S, Mukaiyama T, Sakai K, Asami Y, Kakeya H, Osada H . Asymmetric total synthesis of (−)-azaspirene, a novel angiogenesis inhibitor. J Am Chem Soc 124: 12078–12079 ( 2002)
Mohr P, Tamm C . Biosynthesis of pseurotin A. Tetraherdon 37: 201–212 ( 1981)
Igarashi Y, Yabuta Y, Furumai T . Determination of the absolute configuration of synerazol. J Antibiot 57: 537–540 ( 2004)
Weissman SA, Rossen K, Reider PJ . Stereoselective synthesis of styrene oxides via a Mitsunobu cyclodehydration. Org Lett 3: 2513–2515 ( 2001)
Optical rotation of synthetic 2:[α]D25 (c 0.15, CHC13), natural product [8b]: [α]D25 (c 0.55, CHC13)
Martinelli MJ, Nayyar NK, Moher ED, Dhokte UP, Pawlak JM, Vaidyanathan R . Dibutyltin Oxide Catalyzed Selective Sulfonylation of α-Chelatable Primary Alcohols. Org Lett 1: 447–450 ( 1999)
1H-NMR (400 MHz, CDC13) δ 1.03 (3H, t, J = 7.6 Hz), 1.82 (3H, s), 2.16–2.32 (2H, m), 3.39 (3H, s), 3.73 (1H, d, J = 1.9 Hz), 4.02 (1H, ddd, J = 0.7, 2.0, 7.8 Hz), 4.07 (1H, d, J = 12.7 Hz), 4.63 (1H, d, J = 12.5 Hz), 5.07 (1H, ddt, J = 1.5, 9.0, 10.7 Hz), 5.85 (1H, br dt, J = 11.0, 7.8 Hz), 7.31 (1H, br s), 7.50 (2H, br dd, J = 7.3, 8.3 Hz), 7.65 (1H, br t, J = 7.3 Hz), 8.29 (2H, dd, J = 1.3, 8.3 Hz); 13C-NMR (100 MHz, CDC13) δ 5.1, 14.0, 21.3, 51.7, 53.1, 55.1, 74.0, 89.4, 91.8, 113.8, 123.6, 128.8, 130.5, 132.4, 134.7, 141.3, 164.9, 182.2, 194.2, 196.8; [α]D26 (c 0.075, CHC13), HPLC (Inertsil ODS-2) retention time: 14.9 minutes (synerazol), 15.7 minutes (4).
Chatterjee AK, Grubbs RH . Formal vinyl C–H activation and allylic oxidation by olefin metathesis. Angew Chem Int Ed 41: 3171–3174 ( 2002)
1H-NMR (400 MHz, CDC13) δ 1.70 (3H, s), 2.24 (3H, s), 3.42 (3H, s), 3.62 (1H, br d, J = 7.8 Hz), 3.92 (1H, br d, J = 7.6 Hz), 4.20 (1H, d, J = 12.2 Hz), 4.62–4.68 (1H, m), 4.68 (1H, d, J = 12.2 Hz), 4.75 (1H, br t, J = 6.1 Hz), 6.42 (1H, dd, J = 1.7, 15.7 Hz), 6.88 (1H, dd, 4.4, J = 15.8 Hz), 7.51 (2H, br dd, J = 7.8, 8.0 Hz), 7.66 (1H, br t, J 7.4 Hz), 7.92 (1H, br s), 8.31 (2H, br d, J = 8.0 Hz); 13C-NMR (100 MHz, acetone-d6) δ 5.7, 27.2, 52.2, 72.2, 72.8, 75.4, 92.5, 92.8, 113.8, 129.3, 131.3, 131.5, 134.5, 134.7, 145.5, 167.3, 186.2, 196.2, 197.5, 198.0; [α]D22 (c 0.31, CHC13).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishikawa, M., Ninomiya, T. Chemical Modification of Pseurotin A: One-pot Synthesis of Synerazol and Pseurotin E and Determination of Absolute Stereochemistry of Pseurotin E. J Antibiot 61, 692–695 (2008). https://doi.org/10.1038/ja.2008.99
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2008.99