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

• References and Notes

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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:
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• 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:
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