Synlett, Table of Contents Synlett 2023; 34(06): 673-677DOI: 10.1055/a-1881-0529 cluster Chemical Synthesis and Catalysis in India Synthesis of the Key Skeleton of Phosphoeleganin Authors Gour Hari Mandal Dhiman Saha Sourya Shankar Auddy Rajib Kumar Goswami ∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract The asymmetric synthesis of the key skeleton of phosphoeleganin has been achieved for the first time by using a convergent approach. The salient features of this synthesis include amidation to install a glycine amide at the C-1 position, Wittig olefination to access the C5–C6 bond, Julia–Kocienski olefinations to prepare the C9–C10 and C13–C14 bonds, and a Takai olefination and a Sonogashira coupling to construct the C17–C18 and C18–C19 bonds, respectively. The route disclosed is highly modular, which will permit the synthesis of various analogues, useful for structure–activity relationship studies on phosphoeleganins. Full Text References References and Notes 1a Kato Y, Fusetani N, Matsunaga S, Hashimoto K, Fujita S, Furuya T. J. Am. Chem. Soc. 1986; 108: 2780 1b Boger DL, Hikota M, Lewis BM. J. Org. Chem. 1997; 62: 1748 1c Kohama T, Enokita R, Okazaki T, Miyaoka H, Torikata A, Inukai M, Kaneko I, Kagasaki T, Sakaida Y, Satoh A, Shiraishi A. J. Antibiot. 1993; 46: 1503 1d Thomasi SS, Ladeira C, Ferreira D, da Fontoura Sprenger R, Badino AC, Ferreira AG, Venâncio T. Helv. Chim. Acta 2016; 99: 281 1e Ozasa T, Tanaka K, Sasamata M, Kaniwa H, Shimizu M, Matsumoto H, Iwanami M. J. Antibiot. 1989; 42: 1339 1f Oku N, Takada K, Fuller RW, Wilson JA, Peach ML, Pannell LK, McMahon JB, Gustafson KR. J. Am. Chem. Soc. 2010; 132: 10278 1g Ai Y, Kozytska MV, Zou Y, Khartulyari AS, Smith AB. III. J. Am. Chem. 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Soc. 2004; 126: 12790 14 Mancuso A, Huang S.-L, Swern D. J. Org. Chem. 1978; 43: 2480 15a Hurem D, Dudding T. RSC Adv. 2014; 4: 15552 15b Kim N.-J, Moon H, Park T, Yun H, Jung W.-J, Chang DJ, Kim D.-D, Suh Y.-G. J. Org. Chem. 2010; 75: 7458 15c Brinkmann Y, Oger C, Guy A, Durand T, Galano J.-M. J. Org. Chem. 2010; 75: 2411 16 Compound 2 10% Pd/C (111 mg) was added to a stirred solution of 3 (370 mg, 0.4 mmol) in EtOAc (10 mL), under H2 (balloon) at rt, and the mixture was stirred for 40 h. The mixture was then filtered through a short pad of Celite that was washed with EtOAc (30 mL). The combined organic layers were concentrated under reduced pressure and purified by flash column chromatography [silica gel (100–200 mesh), 20% EtOAc–hexane] to give the corresponding saturated compound as a colorless oil; yield: (202 mg, 58%). Diphenylphosphoryl chloride (30 μl, 0.11 mmol) was added slowly to a solution of the saturated compound (50 mg, 0.055 mmol) in anhyd pyridine (5 mL) at 0 °C under argon, and the mixture was stirred at rt for 48 h. The reaction was quenched with ice–water, and the mixture was extracted with EtOAc (20 mL). The combined organic layers were washed successively with ice–water, 1 N aq HCl, sat. aq NaHCO3, and brine, then dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography [silica gel (100–200 mesh), 15–20% EtOAc–hexane] to give compound 2 as a liquid; yield: 47 mg (72%); [α]D 25 +7 (c 0.8, CHCl3). IR (neat): 3302, 2931 2872, 1733, 1612, 1454, 1388, 1067, 993 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.42–7.05 (m, 12 H), 6.15 (s, 1 H), 4.64–4.46 (m, 1 H), 3.93 (dt, J = 13.0, 5.1 Hz, 4 H), 3.74–3.47 (m, 2 H), 2.62 (t, J = 7.5 Hz, 2 H), 1.77–1.66 (m, 5 H), 1.42–1.20 (m, 62 H), 0.89–0.86 (m, 15 H), 0.15–0.06 (m, 12 H). 13C NMR (75 MHz, CDCl3): δ = 158.0, 155.8, 151.0, 150.9, 150.8, 129.8, 125.3, 125.2, 120.4, 120.3, 120.2, 108.0, 107.6, 84.9, 84.8, 83.4, 78.6, 78.4, 77.4, 74.4, 74.3, 72.3, 37.4, 33.8, 32.1, 30.4, 30.3, 30.2, 29.9, 29.8, 29.8, 29.7, 29.6, 29.5, 29.3, 28.8, 28.7, 28.2, 27.0, 26.4, 26.1, 26.1, 25.9, 25.5, 25.2, 22.9, 18.4, 18.3, 14.3, 1.2, 0.2, –4.1, –4.2, –4.3, –4.4. HRMS (ESI): m/z [M + H + Na]+ calcd for C63H112NNaO11PSi2: 1169.7487; found: 1169.779. Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
