Stereoselective Synthesis of Volicitin and 9-D ₁-Volicitin

Abstract

The synthesis of volicitin involved the condensation of l-(+)-glutamine with 17(S)-hydroxylinolenoic acid, derived from a Wittig reaction between the C10–C18 phosphonium salt and the C1–C9 aldehyde. The phosphonium salt was prepared through the alkynylation of a (Z)-allylic phosphate with an alkyne derived from (2S)-but-3-yn-2-ol. The deuterated aldehyde was derived with a 96% deuteration ratio by reduction of the C1–C9 methyl ester with NaBD₄, followed by oxidation. Subsequently, 9-D ₁-volicitin was synthesized from the monodeuterated aldehyde by using the Wittig reaction and condensation with l-(+)-glutamine.

Key words

volicitin - deuteration - alkynylation - Wittig reaction - condensation

Publication History

Received: 07 November 2023

Accepted after revision: 04 December 2023

Article published online:
15 January 2024

• References and Notes

• 1a Alborn HT, Turlings TC. J, Jones TH, Stenhagen G, Loughrin JH, Tumlinson JH. Science 1997; 276: 945
• 1b Paré PW, Alborn HT, Tumlinson JH. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13971
• 2a Paré PW. Tumlinson J. H. Plant Physiol. 1997; 114: 1161
• 2b Frey M, Stettner C, Paré PW, Schmelz EA, Tumlinson JH, Gierl A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 14801
• 2c Shen B, Zheng Z, Dooner HK. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 14807
• 3a Pohnert G, Koch T, Boland W. Chem. Commun. 1999; 1087
• 3b Hansen TV, Stenstrom Y. Synth. Commun. 2000; 30: 2549
• 3c Wei H.-X, Truitt CL, Paré PW. Tetrahedron Lett. 2003; 44: 831
• 3d Krishnamachari V, Xie X, Zhu S, Wei H.-X, Paré PW. Nat. Prod. Commun. 2007; 2: 1019
• 4a Ogawa N, Katagiri K, Haimoto Y, Kobayashi Y. Org. Biomol. Chem. 2022; 20: 4338
• 4b Ogawa N, Arai K, Kobayashi Y. Synlett 2022; 33: 76
• 4c Ogawa N, Amano T, Kobayashi Y. Synlett 2021; 32: 295
• 4d Ogawa N, Sone S, Hong S, Lu Y, Kobayashi Y. Synlett 2020; 31: 1735
• 5 Mamada S, Ogawa N. Eur. J. Org. Chem. 2023; e202300056
• 6a Watanabe A, Hama K, Watanabe K, Fujiwara Y, Yokoyama K, Murata S, Takita R. Angew. Chem. Int. Ed. 2022; 61: e202202779
• 6b Egoshi S, Dodo K, Ohgane K, Sodeoka M. Org. Biomol. Chem. 2021; 19: 8232
• 6c Dodo K, Sato A, Tamura Y, Egoshi S, Fujiwara K, Oonuma K, Terayama N, Sodeoka M. Chem. Commun. 2021; 57: 2180
• 6d Firsov AM, Fomich MA, Bekish AV, Sharko OL, Kotova EA, Saal HJ, Vidovic D, Shmanai VV, Pratt DA, Antonenko YN, Shchepinov MS. FEBS J. 2019; 286: 2099
• 6e Navratil AR, Shchepinov MS, Dennis EA. J. Am. Chem. Soc. 2018; 140: 235
• 6f Fomich MA, Bekish AV, Vidovic D, Lamberson CR, Lysenko IL, Lawrence P, Brenna JT, Sharko OL, Shmanai VV, Shchepinov MS. ChemistrySelect 2016; 1: 4758
• 6g Hill S, Lamberson CR, Xu L, To R, Tsui HS, Shmanai VV, Bekish AV, Awad AM, Marbois BN, Cantor CR, Porter NA, Clarke CF, Shchepinov MS. Free Radical Biol. Med. 2012; 53: 893
• 6h McGinley CM, van der Donk WA. J. Labelled Compd. Radiopharm. 2006; 49: 545
• 7 Raghavan S, Patel JS, Ramakrishna KV. S. RSC Adv. 2016; 6: 72877
• 8 Gagestein B, von Hegedus JH, Kwekkeboom JC, Heijink M, Blomberg N, van der Wel T, Florea BI, van den Elst H, Wals K, Overkleeft HS, Giera M, Toes RE. M, Ioan-Facsinay A, van der Stelt M. J. Am. Chem. Soc. 2022; 144: 18938
• 9a Brown CA, Ahuja VK. J. Chem. Soc., Chem. Commun. 1973; 553
• 9b Brown CA, Ahuja VK. J. Org. Chem. 1973; 38: 2226
• 10 Schulthoff S, Hamilton JY, Heinrich M, Kwon Y, Wirtz C, Fürstner A. Angew. Chem. Int. Ed. 2021; 60: 446
• 11 Tonoi T, Inohana T, Kawahara R, Sato T, Ikeda M, Akutsu M, Murata T, Shiina I. ACS Omega 2021; 6: 3571
• 12 The ¹H and ¹³C NMR spectra of the Wittig product indicated a high Z-selectivity for the Wittig reaction.
• 13 Ishiwata H, Sone H, Kigoshi H, Yamada K. Tetrahedron 1994; 50: 12853
• 14 Fortunati T, D’Acunto M, Caruso T, Spinella A. Tetrahedron 2015; 71: 2357
• 15 Volicitin (1) To an ice-cold solution of carboxylic acid 2 (83.1 mg 0.282 mmol) in THF (2.8 mL) was added Et₃N (0.047 mL, 0.34 mmol). After 1 h at 0 °C, ClCO₂Et (0.032 mL, 0.034 mmol) was added to the mixture. After a further 1 h at 0 °C, a solution of l-(+)-glutamine (53.5 mg, 0.367 mmol) in aq NaOH was added to the mixture. After 1.5 h at r.t., the mixture was diluted with 3 N aq HCl and extracted with EtOAc (×3). The combined extracts were dried (MgSO₄) and concentrated. The residue was semi-purified by chromatography (silica gel, EtOAc to EtOAc–MeOH) to give crude 1. The crude 1 was purified by chromatography (Wakosil 50C18, MeCN–H₂O) to give a white amorphous solid; yield: 81.8 mg (69%); R_f = 0.09 (EtOAc–MeOH, 2:1); [α]_D ²⁷ +8 (c 0.095, MeOH), [α]_D ²⁶ +2 (c 0.26, CH₂Cl₂) [Lit.^3a [α]_D ²² +3 (c 0.83, CH₂Cl₂)]. IR (neat): 3472, 1715, 1670, 1450, 670 cm^–1. ¹H NMR (400 MHz, CD₃OD): δ = 1.11 (d, J = 6.4 Hz, 3 H), 1.21–1.31 (m, 8 H), 1.54 (t, J = 7.2 Hz, 2 H), 1.81–1.90 (m, 1 H), 1.99 (q, J = 6.4 Hz, 2 H), 2.03–2.13 (m, 1 H), 2.16 (t, J = 7.6 Hz, 2 H), 2.18–2.23 (m, 2 H), 2.73 (t, J = 6.0 Hz, 2 H), 2.78 (t, J = 6.0 Hz, 2 H), 4.26 (dd, J = 8.8, 5.2 Hz, 1 H), 4.54 (quint, J = 6.4 Hz, 1 H), 5.20–5.36 (m, 6 H). ¹³C NMR (100 MHz, CD₃OD): δ = 24.0, 26.5, 26.8, 26.9, 28.1, 28.8, 30.21, 30.26, 30.32, 30.7, 32.8, 36.9, 53.6, 64.3, 128.6, 129.1, 129.6, 131.2, 135.4, 175.6, 176.2, 177.8. HRMS (FD): m/z [M⁺] calcd for C₂₃H₃₈N₂O₅: 422.27807; found: 422.27801.