Special Issue Honoring Masahiro Murakami’s Contributions to Science
Total Syntheses of Dysidealactams E and F and Dysidealactone B, Drimane-Type Sesquiterpenes Derived from a Dysidea sp. of Marine Sponge
Yuhao Chen
a
Guangdong Key Laboratory for Research and the Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, P. R. of China
,
Ping Lan
b
Institute for Advanced and Applied Chemical Synthesis, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P. R. of China
,
Lorenzo V. White
b
Institute for Advanced and Applied Chemical Synthesis, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P. R. of China
,
Weiguang Yang∗
a
Guangdong Key Laboratory for Research and the Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, P. R. of China
a
Guangdong Key Laboratory for Research and the Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, P. R. of China
b
Institute for Advanced and Applied Chemical Synthesis, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P. R. of China
› InstitutsangabenWe thank the National Natural Science Foundation of China (Grant Nos. 22250410258 and 22250410259), the Science and Technology Planning Program of Zhanjiang (Grant. No. 2021A05247) and the Ministry of Science and Technology of the People’s Republic of China for financial support.
Dedicated to Professor Masahiro Murakami (Kyoto University) in recognition of his profound and ingenious contributions to so many aspects of chemical synthesis.
Abstract
Dysidealactams E and F and dysidealactone B are recently reported marine natural products. Their syntheses from β-cyclocitral are detailed here. The preparation of certain derivatives and analogues of these compounds is also described and single-crystal X-ray analyses of two of these, as well as that of (±)-dysidealactam F, are reported.
5 Dysidealactone A (6) and dysidealactone B (7) also appear to have been isolated from the New Caledonian sponge Dysidea fusca; see:
Montagnac A,
Martin M.-T,
Debitus C,
Païs M.
J. Nat. Prod. 1996; 59: 866
13 As a referee has pointed out, the aromatization process leading to byproduct 13 is most likely the result of a radical-chain process whereby an initiating radical abstracts the doubly allylic hydrogen from cycloadduct 12, and the ensuing cyclohexadienyl radical then undergoes aromatization by elimination of a methyl radical. The latter, in turn, abstracts the doubly allylic hydrogen of another molecule of 12, thereby propagating the chain; see:
Walton JC,
Studer A.
Acc. Chem. Res. 2005; 38: 794
14 CCDC 2220506, 2220507, and 2220508 contain the supplementary crystallographic data for compounds (±)-5, (±)-8, and (±)-18. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
16(±)-[(5aS,9aS)-6,6,9a-Trimethyl-1,3-dioxo-1,3,4,5,5a,6,7,8,9,9a-decahydro-2H-benzo[e]isoindol-2-yl]acetic acid [(±)-4]
A Schlenk tube equipped with a magnetic stirrer bar was charged with compound (±)-8 (500 mg, 2.01 mmol), glycine (1.51 g, 20.1 mmol), and 1:1 MeCN–H2O (6.0 mL). The tube was sealed and the contents were heated at 105 °C (oil-bath temperature) for 8 h. The cooled mixture was then diluted with H2O (10 mL) and the separated aqueous phase was extracted with EtOAc (3 × 25 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure and the resulting residue was subjected to flash chromatography [silica gel, EtOAc–PE (1:3 + 1% AcOH)] to afford, after concentration of the appropriate fractions, a clear yellow oil; yield: 331 mg (54%); Rf = 0.3 (1:3 EtOAc–PE +1% AcOH).
FTIR (ATR): 2930, 1703, 1420, 1391, 1233, 1207, 1117, 937, 735 cm–1. 1H NMR (400 MHz, CD3OD): δ = 4.13 (s, 2 H), 2.50 (d, J = 14.0 Hz, 2 H), 2.25 (m, 1 H), 1.97 (m, 1 H), 1.76 (m, 1 H), 1.63–1.45 (complex m, 3 H), 1.38–1.25 (complex m, 3 H), 1.23 (s, 3 H), 0.96 (s, 3 H), 0.93 (s, 3 H); COOH proton not observed. 13C{1H} NMR (100 MHz, CD3OD): δ = 171.8, 171.5, 170.9, 151.4, 141.5, 53.2, 42.9, 39.2, 37.6, 36.3, 34.4, 33.9, 23.0, 22.0, 21.1, 19.5, 19.0. HRMS (TOF ESI, +): m/z [M + H]+ calcd for C17H24NO4: 306.1705; found: 306.1714.
17 For a related example of the use of urea as an ammonia surrogate, see:
Naidu PP,
Raghunadh A,
Rao KR,
Mekala R,
Babu JM,
Rao BR,
Siddaiah V,
Pal M.
Synth. Commun. 2014; 44: 1475
21 For a conceptually related approach using the naturally derived drimane polygodial, see:
Rhak KJ,
Bissember AC,
Smith JA.
Tetrahedron 2018; 74: 1167
22 For a chiral-auxiliary-based method leading to the formation of homochiral Diels–Alder adducts of diene 10, see:
Hendersen JR,
Parvez M,
Keay BA.
Org. Lett. 2009; 11: 3178