Synthesis of the C1–C13 Segment of Poecillastrin C

Abstract

A stereoselective synthesis of the C1–C13 segment of poecillastrin C has been achieved. The C1–C4 moiety was derived from diallyl l-tartrate, and the amide group at the C3 position was constructed by means of a traceless Staudinger reaction. The C1–C13 segment was submitted to model studies, including esterification with a bulky alcohol at the C1 position and Stille coupling with vinyl iodide at the C13 position. The reactivity of the C1 position was affected by the neighboring C2-protective group. When the C2 hydroxy group was protected as a TBS ether, the C1 carboxylic acid did not undergo esterification with a bulky secondary alcohol, whereas the p-methoxybenzylidene N,O-acetal afforded a 2,4-dimethyl-3-pentyl ester. Stille coupling of the C1–C13 segment with 1-iodohept-1-ene gave the southern part of the poecillastrin C macrolactam attached to simplified eastern and western parts.

Key words

stereoselective synthesis - hydroxyaspartic acid - Staudinger reaction - poecillastrin

Publication History

Received: 22 November 2023

Accepted after revision: 04 December 2023

Accepted Manuscript online:
04 December 2023

Article published online:
05 January 2024

• References and Notes

• 1 Takada K, Choi BW, Rashid MA, Gamble WR, Cardellina JH. II, Van Q N, Lloyd JR, McMahon JB, Gustafson KR. J. Nat. Prod. 2007; 70: 428
• 2 Takemoto D, Takekawa Y, van Soest RW. M, Fusetani N, Matsunaga S. Biosci., Biotechnol., Biochem. 2007; 71: 2697
• 3 Irie R, Takada K, Ise Y, Ohtsuka S, Okada S, Gustafson KR, Matsunaga S. Org. Lett. 2017; 19: 5395
• 4a Irie R, Hirota Y, Ise Y, Okada S, Takada K, Matsunaga S. Tetrahedron 2018; 74: 1430
• 4b Suo R, Takada K, Irie R, Watanabe R, Suzuki T, Ise Y, Ohtsuka S, Okada S, Matsunaga S. J. Nat. Prod. 2018; 81: 1295

The Cossy group has reported synthetic studies on mirabalin, an analogue of poecillastrins, for which a partial absolute structure has been reported, and they have proceeded with synthetic studies of mirabalin with arbitrarily assigned configurations of the unknown stereocenters; see:
• 5a Echeverria P.-G, Pons A, Prévost S, Férard C, Cornil J, Guérinot A, Cossy J, Phansavath P, Ratovelomanana-Vidal V. ARKIVOC 2019; (iv): 44
• 5b Cornil J, Echeverria P.-G, Reymond S, Phansavath P, Ratovelomanana-Vidal V, Guérinot A, Cossy J. Org. Lett. 2016; 18: 4534
• 5c Echeverria P.-G, Prévost S, Cornil J, Férard C, Reymond S, Guérinot A, Cossy J, Ratovelomanana-Vidal V, Phansavath P. Org. Lett. 2014; 16: 2390
• 6 For a related reaction, see: Isobe T, Ishikawa T. J. Org. Chem. 1999; 64: 6989
• 7 Saxon E, Armstrong JI, Bertozzi CR. Org. Lett. 2000; 2: 2141
• 8 Phillips EM, Mesganaw T, Patel A, Duttwyler S, Mercado BQ, Houk KN, Ellman JA. Angew. Chem. Int. Ed. 2015; 54: 12044
• 9 Breuning A, Vicik R, Schirmeister T. Tetrahedron: Asymmetry 2003; 14: 3301
• 10 Kapadnis PB, Hall E, Ramstedt M, Galloway WR. J. D, Welch M, Spring DR. Chem. Commun. 2009; 538
• 11 Saito S, Komada K, Moriwake T. Org. Synth. 1996; 73: 184
• 12 The absolute configuration at the C3 position of azide 9 was determined by the Mosher method after reduction of the azide group to the corresponding amine; see the Supporting Information.
• 13 Amide 23 Phosphine 14 (114 mg, 0.278 mmol) was added to a solution of compound 15 (96.0 mg, 0.280 mmol) in DMF (1.6 mL) and H₂O (270 μL), and the mixture was stirred for 15 h at 70 ℃, then cooled to rt. EtOAc (5.0 mL) and H₂O (5.0 mL) were added, and then the layers were separated. The aqueous layer was extracted with EtOAc (2 × 5.0 mL), and the combined organic layer was dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (5:1)] to give a colorless oil; yield: 69.0 mg (0.153 mmol, 55%); R_f = 0.55 (hexane–EtOAc, 4:1); [α]_D ²⁴ +3.5 (c 1.20, MeOH). IR (thin film, KBr): 3309, 2954, 2930, 2858, 1755, 1671, 1501, 1253, 1135, 996, 908, 837, 727, 646 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.19 (dd, J = 15.5, 11.0 Hz, 1 H), 6.22 (dd, J = 15.5, 11.0 Hz, 1 H), 6.13 (d, J = 10.0 Hz, 1 H), 6.10 (dt, J = 15.5, 6.5 Hz, 1 H), 5.88 (d, J = 15.5 Hz, 1 H), 5.87 (dddd, J = 17.5, 10.5, 6.0, 6.0 Hz, 1 H), 5.31 (dddd, J = 17.5, 1.5, 1.5, 1.5 Hz, 1 H), 5.23 (dddd, J = 10.5, 1.5, 1.5, 1.5 Hz, 1 H), 5.21 (dd, J = 10.0, 2.0 Hz, 1 H), 4.85 (d, J = 2.0 Hz, 1 H) , 4.62 (dddd, J = 13.0, 6.0, 1.5, 1.5 Hz, 1 H), 4.57 (dddd, J = 13.0, 6.0, 1.5, 1.5 Hz, 1 H), 3.75 (s, 3 H), 2.39 (dt, J = 6.5, 6.5 Hz, 2 H), 2.34–2.29 (m, 2 H), 1.98 (t, J = 2.5 Hz, 1 H), 0.88 (s, 9 H), 0.11 (s, 3 H), 0.02 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.9, 169.6, 165.9, 141.8, 140.6, 131.4, 129.4, 121.9, 119.1, 83.2, 72.3, 69.1, 66.2, 55.5, 52.7, 31.7, 25.5, 18.2, 18.1, –4.8, –5.9. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₃₅NNaO₆Si: 472.2126; found: 472.2127.
• 14 The absolute configuration at the C2 position of alcohol 24 was confirmed by degradation with 6 M HCl to give the known (2R,3R)-3-hydroxyaspartic acid hydrochloride salt.
• 15 (2R,3R)-3-Hydroxyaspartic Acid Hydrochloride Salt by Acid Hydrolysis of Amide 24 Compound 24 (114 mg, 0.359 mmol) was dissolved in 6 M HCl (7.2 mL), and the solution was refluxed for 12 h. The resulting mixture was cooled to r.t. and CH₂Cl₂ (6 mL) was added. The layers were separated, and the aqueous layer was washed with CH₂Cl₂ (3 × 6 mL) to remove all organic impurities. The aqueous layer was concentrated under reduced pressure to give a white solid; yield: 60.1 mg (0.324 mmol, 90%); R_f = 0.30 (CHCl₃–MeOH–H₂O, 4:4:1); [α]_D ²⁴ +20.4 (c 0.98, H₂O), [α]_D ²⁴ –1.7 (c 1.01, 5 M aq HCl). ¹H NMR (400 MHz, D₂O): δ = 4.88 (d, J = 2.5 Hz, 1 H), 4.43 (d, J = 2.5 Hz, 1 H). ¹³C NMR (100 MHz, D₂O) [acetone (30.89 ppm) as internal standard]: δ = 173.6, 170.0, 69.0, 55.8.

For (2R,3R)-3-hydroxyaspartic acid hydrochloride salt, see:
• 16a Khalaf JK, Datta A. Amino Acids 2008; 35: 507
• 16b Okai H, Imamura N, Izumiya N. Bull. Chem. Soc. Jpn. 1967; 40: 2154
• 17 Zhang HX, Guibé F, Balavoine G. Tetrahedron Lett. 1988; 29: 623
• 18 Saitoh K, Shiina I, Mukaiyama T. Chem. Lett. 1998; 679
• 19 Darwish A, Lang A, Kim T, Chong JM. Org. Lett. 2008; 10: 861
• 20 Zhang HX, Guibé F, Balavoine G. J. Org. Chem. 1990; 55: 1857
• 21a Matsumoto Y, Hibino K, Yonaga M, Kakeya H, Hayashi Y. Org. Lett. 2016; 18: 3382
• 21b Farina V, Krishnan B. J. Am. Chem. Soc. 1991; 113: 9585