Synlett 2019; 30(11): 1346-1350
DOI: 10.1055/s-0037-1611559
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a C1–C12 Fragment of Gulmirecin B

Rathikrishnan Rengarasu
,
Financial support by the state of Baden-Württemberg is gratefully acknowledged.
Weitere Informationen

Publikationsverlauf

Received: 14. Februar 2019

Accepted after revision: 03. Mai 2019

Publikationsdatum:
22. Mai 2019 (online)


Abstract

The synthesis of a C1–C14 fragment of the macrolide antibiotic gulmirecin B through formation of the C7–C8 bond by addition of a vinyllithium intermediate to a C1–C7 aldehyde was investigated. This crucial coupling was successful with a vinyllithium reagent corresponding to a C8–C12 fragment. The C8–C12 vinyl bromide was prepared from l-malic acid. The C1–C7 aldehyde building block was synthesized from hex-5-enoic acid by using an Evans alkylation, a cross-metathesis, and an asymmetric dihydroxylation as key steps.

Supporting Information

 
  • References and Notes

  • 1 Schieferdecker S, König S, Weigel C, Dahse H.-M, Werz O, Nett M. Chem. Eur. J. 2014; 20: 15933
  • 2 Surup F, Viehrig K, Mohr KI, Herrmann J, Jansen R, Müller R. Angew. Chem. Int. Ed. 2014; 53: 13588
  • 3 Kwon Y, Schulthoff S, Dao QM, Wirtz C, Fürstner A. Chem. Eur. J. 2018; 24: 109
    • 4a Wolling M, Kirschning A. Eur. J. Org. Chem. 2018; 648
    • 4b Surup F, Steinmetz H, Mohr K, Viehrig K, Müller R, Nett M, Schieferdecker S, Dahse H.-M, Wolling M, Kirschning A. WO 2016005049, 2016
  • 5 Hanessian S, Ugolini A, Dubé D, Glamyan A. Can. J. Chem. 1984; 62: 2146
  • 6 Yadav JS, Gopala Rao Y, Ravindar K, Subba Reddy BV, Narsaiah AV. Synthesis 2009; 3157
  • 7 Smith AB. III, Chen SS.-Y, Nelson FC, Reichert JM, Salvatore BA. J. Am. Chem. Soc. 1997; 119: 10935
  • 9 For a related procedure, see: Imagawa H, Tsuchihashi T, Singh RK, Yamamoto H, Sugihara T, Nishizawa M. Org. Lett. 2003; 5: 153
  • 10 For a related Wittig reaction on an α-(trialkylsilyloxy)methyl ketone, see: Jung ME, van den Heuvel A, Leach AG, Houk KN. Org. Lett. 2003; 5: 3375
    • 11a Sánchez LG, Castillo EN, Maldonado H, Chávez D, Somanathan R, Aguirre G. Synth. Commun. 2007; 38: 54
    • 11b Ogibin YN, Starostin EK, Aleksandrov AV, Pivnitsky KK, Nikishin GI. Synthesis 1994; 901
    • 12a Ghosh AK, Gong G. J. Org. Chem. 2006; 71: 1085
    • 12b Kaliappan KP, Ravikumar V. J. Org. Chem. 2007; 72: 6116
    • 12c Taaning RH, Thim L, Karaffa J, Campaña AG, Hansen A.-M, Skrydstrup T. Tetrahedron 2008; 64: 11884
    • 14a Hiebel M.-A, Pelotier B, Piva O. Tetrahedron Lett. 2010; 51: 5091
    • 14b Tomas L, Boije af Gennäs G, Hiebel MA, Hampson P, Gueyrard D, Pelotier B, Yli-Kauhaluoma J, Piva O, Lord JM, Goekjian PG. Chem. Eur. J. 2012; 18: 7452
  • 15 Chatterjee AK, Choi T.-L, Sanders DP, Grubbs RH. J. Am. Chem. Soc. 2003; 125: 11360
  • 16 Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
  • 17 C1C12 fragment 39 Vinyl bromide 22 (0.15 g, 0.25 mmol) was dried by dissolving it in a 1:1 mixture of benzene and toluene (3 mL), followed by evaporation of the solvents using a Rotavapor and placing the residue under a high vacuum for 1 h. THF (1.5 mL) was then added under argon and the flask was cooled to –78 °C. A 1.4 M solution of s-BuLi in cyclohexane (0.21 mL, 0.30 mmol) was added dropwise and the mixture was stirred for 30 min at –78 °C before a solution of aldehyde 37 (0.14 g, 0.43 mmol) in THF (1.5 mL) was added dropwise. After completion of the addition, the mixture was stirred at –78 °C for 2 h and then at r.t. for 1 h. Finally, the mixture was treated with sat. aq NH4Cl solution (5 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2 × 8 mL). The combined organic layers were washed with sat. aq NaCl (5 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude allylic alcohol 39 (yield: 86 mg; dr = 10:4) was used in the next reaction without chromatographic purification. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C53H74NaO7Si: 873.5094; found: 873.5094. Enone 40 DMP (70 mg, 0.16 mmol) and NaHCO3 (20 mg, 0.24 mmol) were added to a solution of alcohol 39 (70 mg, 0.08 mmol) in CH2Cl2 (5 mL) at 0 °C. The cooling bath was then removed and the mixture was stirred for 2 h at r.t. The mixture was diluted with sat. aq NaHCO3 (5 mL), the layers were separated, and the aqueous layer was extracted with CH2Cl2 (2 × 5 mL). The combined organic layers were washed with sat. aq NaCl (8 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography [silica gel, PE–EtOAc (85:15)] to give a colorless oil; yield: 50 mg (71%); Rf = 0.48 (PE–EtOAc, 9:1); [α]D 19 –6.85 (c = 0.52, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.7 Hz, 3 H, 2-CH3), 0.94–0.96 {m, 21 H, Si[CH(CH3)2]3}, 1.25–1.30 (m, 1 H, 3-H), 1.30 [s, 3 H, C(CH3)2], 1.37–1.44 [m, 4 H, C(CH3)2, 3-H], 1.50–1.53 (m, 1 H, 4-H), 1.56–1.60 (m, 1 H, 4-H), 1.68–1.73 (m, 1 H, 2-H), 1.80 (s, 3 H, 8-CH3), 2.70–2.73 (m, 2 H, 10-H), 2.97 (t, J = 8.3 Hz, 1 H, 12-H), 3.10–3.20 (m, 2 H, 12-H, 1-H), 3.26 (dd, J = 9.0, 5.8 Hz, 1 H, 1-H), 3.77 (s, 3 H, OCH3), 4.10–4.18 (m, 1 H, 11-H), 4.22–4.26 (m, 1 H, 5-H), 4.34 (d, J = 7.4 Hz, 1 H, 6-H), 4.48 (d, J = 1.8 Hz, 2 H, CH2Ar), 6.86 (d, J = 8.6 Hz, 2 H, ArH), 6.97 (t, J = 6.4 Hz, 1 H, 9-H), 7.17–7.27 (m, 12 H, ArH), 7.38–7.41 (m, 5 H, ArH). 13C NMR (100 MHz, CDCl3): δ = 11.8 (8-CH3), 12.3 {Si[CH(CH3)2]3}, 16.9 (2-CH3), 18.0 {Si[CH(CH3)2]3}, 26.2 [C(CH3)2], 27.2 [C(CH3)2], 29.7 (C-3), 30.6 (C-4), 33.4 (C-2), 34.8 (C-1), 55.2 (OCH3), 66.3 (C-12), 70.3 (C-11), 72.6 (CH2Ar), 75.5 (C-1), 78.0 (C-5 or C-6), 80.3 (C-6 or C-5), 86.6 (CPh3), 109.8 [C(CH3)2], 113.7, 127.0, 127.7, 128.6, 129.0, 130.8 (6 × Ar), 137.7 (C-8), 142.5 (C-9), 143.9 (Ar C), 159.0 (Ar C), 197.5 (C-7). HRMS (ESI-TOF): m/z [M + Na]+ calcd for C53H72NaO7Si: 871.4929; found: 871.4929.
  • 18 Edwards JT, Merchant RR, McClymont KS, Knouse KW, Qin T, Malins LR, Vokits B, Shaw SA, Bao D.-H, Wei F.-L, Zhou T, Eastgate MD, Baran PS. Nature 2017; 545: 213