Synthesis of the All-l Cyclopentapeptides Versicoloritides A, B, and C

Abstract

Herein we describe the first synthesis of the all-l naturally occurring cyclopentapeptides versicoloritides A, B, and C. We found that the extent of oligomerization and epimerization upon head-to-tail cyclization of the linear pentapeptide precursors could be reduced to acceptable levels by modifying the reaction conditions.

Key words

cyclic peptides - versicoloritides - natural products - ­cyclization - total synthesis

• References and Notes

• 1 Zhuang YB, Teng XC, Wang Y, Liu PP, Wang H, Li J, Li GQ, Zhu WM. Tetrahedron 2011; 67: 7085
• 2a Houston DR, Shiomi K, Arai N, Omura S, Peter MG, Turberg A, Synstad B, Eijsink VG. H, van Aalten DM. F. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 9127
• 2b Wu W, Dai HQ, Bao L, Ren BA, Lu JC, Luo YM, Guo LD, Zhang LX, Liu HW. J. Nat. Prod. 2011; 74: 1303
• 2c Fremlin LJ, Piggott AM, Lacey E, Capon RJ. J. Nat. Prod. 2009; 72: 666
• 3a Schmidt U, Langner J. J. Pept. Res. 1997; 49: 67
• 3b Li F, Zhang FM, Bin Yang Y, Yang XQ, Cao QE, Ding ZT. Chin. Chem. Lett. 2008; 19: 193
• 3c Tang YC, Xie HB, Tian GL, Ye YH. J. Pept. Res. 2002; 60: 95
• 4a White CJ, Yudin AK. Nat. Chem. 2011; 3: 509
• 4b Ehrlich A, Heyne HU, Winter R, Beyermann M, Haber H, Carpino LA, Bienert M. J. Org. Chem. 1996; 61: 8831
• 4c Kaur H, Heapy AM, Brimble MA. Synlett 2012; 23: 275
• 5 Davies JS. J. Pept. Sci. 2003; 9: 471
• 6 Malesevic M, Strijowski U, Bachle D, Sewald N. J. Biotechnol. 2004; 112: 73
• 7a Carpino LA, Elfaham A, Albericio F. Tetrahedron Lett. 1994; 35: 2279
• 7b Ye YH, Gao XM, Liu M, Tang YC, Tian GL. Lett. Pept. Sci. 2003; 10: 571
• 8 Jiang S, Li Z, Ding K, Roller PP. Curr. Org. Chem. 2008; 12: 1502
• 9 Rizo J, Gierasch LM. Annu. Rev. Biochem. 1992; 61: 387
• 10 Harris PW. R, Brimble MA. Synthesis 2009; 3460
• 11a Blanchette JP, Ferland P, Voyer N. Tetrahedron Lett. 2007; 48: 4929
• 11b Li P, Roller PP, Xu JC. Curr. Org. Chem. 2002; 6: 411
• 12 Marcucci E, Tulla-Puche J, Albericio F. Org. Lett. 2012; 14: 612
• 13 Versicoloritide B (2) To a solution of DIPEA (28 μL, 161 μmol) in CH₂Cl₂ (36 mL) was added 5 (18 mg, 32 μmol) and HBTU (36 mg, 95 μmol) in CH₂Cl₂–DMF (4:1, 15 mL) at 0.5 mL/h. The reaction mixture was concentrated under reduced pressure, diluted with 0.1% TFA–H₂O (v/v, 18 mL), and purified by RP-HPLC to afford 2 as a colorless solid (10 mg, 57%). HRMS (EI): m/z [M + Na]⁺ calcd for C₃₀H₃₅N₅NaO₅: 568.2536; found: 568.2526. IR: 3277, 2956, 1626, 1542, 1447, 1344, 1162, 746, 702 cm^–1. [α]_D ²⁰ –46 (c 0.1, MeOH) [lit. –43.6 (c 0.1, MeOH)].¹ See the Supporting Information for complete procedures and analytical data
• 14a Wele A, Mayer C, Derinigny Q, Zhang Y, Blond A, Bodo B. Tetrahedron 2008; 64: 154
• 14b Schmidt G, Grube A, Kock M. Eur. J. Org. Chem. 2007; 4103
• 15 Versicoloritide A (1) To a solution of DIPEA (31 μL, 178 μmol) in CH₂Cl₂ (44 mL) was added 4 (22 mg, 38 μmol), HBTU (44 mg, 116 μmol), and HOBt (15 mg, 111 μmol) in CH₂Cl₂–DMF (4.7:1, 17 mL) at 0.5 mL/h. The reaction mixture was concentrated under reduced pressure, diluted with 0.1% TFA–H₂O (v/v, 10 mL) and purified by RP-HPLC to 1 as a colorless solid (5.5 mg, 26%). HRMS (EI): m/z [M + Na]⁺ calcd for C₃₁H₃₇N₅NaO₅: 582.2692; found: 582.2675. IR: 3280, 2937, 1633, 1519, 1448, 1346, 1319, 1161, 745, 701 cm^–1. [α]_D ²⁰ –122 (c 0.1, MeOH) [lit. –90.7 (c 1.7, MeOH)].¹ See the Supporting Information for complete procedures and analytical data
• 16a Francart C, Wieruszeski JM, Tartar A, Lippens G. J. Am. Chem. Soc. 1996; 118: 7019
• 16b Gesquiere JC, Diesis E, Cung MT, Tartar A. J. Chromatogr. 1989; 478: 121
• 17 Yoshiya T, Kawashima H, Hasegawa Y, Okamoto K, Kimura T, Sohma Y, Kiso Y. J. Pept. Sci. 2010; 16: 437
• 18a Han SY, Kim YA. Tetrahedron 2004; 60: 2447
• 18b Carpino LA, Elfaham A. J. Org. Chem. 1994; 59: 695
• 19 Ye YH, Li HT, Jiang XH. Biopolymers 2005; 80: 172
• 20 Versicoloritide C (3) To a solution of DIPEA (60 μL, 344 μmol) in CH₂Cl₂ (80 mL) was added 6 (40 mg, 67 μmol) and HBTU (77 mg, 200 μmol) in CH₂Cl₂–DMF (5:1, 22 mL) at 0.5 mL/h. After complete addition of the reagents, the reaction mixture was concentrated under reduced pressure, diluted with 0.1% TFA–H₂O (v/v, 18 mL), and purified by RP-HPLC to afford 3 as a colorless solid (17 mg, 44%). HRMS (EI): m/z [M + Na]⁺ calcd for C₃₁H₃₇N₅NaO₆: 598.2642; found: 598.2645. IR: 3307, 2956, 1632, 1523, 1443, 1345, 1165, 746, 700 cm^–1. [α]_D ²⁰ –135.5 (c 0.2, MeOH) [lit. –118 (c 0.2, MeOH)].¹ See Supporting Information for complete procedures and analytical data