Synthesis of hyperolactones A and C

Abstract

Hyperolactones A (1) and C (3) have been synthesized starting from (S)-malic acid by a straightforward route. The unique spirolactone skeleton was efficiently constructed by one-pot reaction as a key step. The absolute stereochemistry of hyperolactones was unambiguously established by this synthesis. (2) and (-)-hyperolactone C (3), were also isolated from the same plant as minor components in 1995 [2]. The gross structure of 1 and its relative stereochemistry were determined by means of extensive spectroscopic studies and chemical transformation, and was finally confirmed by X-ray crystallographic analysis. These compounds possess a common spirolactone skeleton (anti-orientation at the stereogenic center C-5 in 2 as compared with 1 and 3), and some novel characteristics of the structure are (1) a highly substituted 1,7-dioxaspiro[4,4]non-2-ene-4,6-dione skeleton; (2) a strained 2,2,5-trisubstituted 3(2H)furanone ring system. Owing to their structural uniqueness, compound 1 and structurally related natural products are good targets for total synthesis [3]. We now describe herein the synthesis of 1 and 3 in a stereoselective fashion, which enables us to establish their absolute stereochemistry unambiguously. Synthesis of the Side Chain Units 8 and 14.The requisite aldehyde 8 was synthesized as shown in Scheme 1. The β-keto ester 6 was obtained by the Collins oxidation of the β-hydroxy ester 5, which was prepared from ethyl bromoacetate and benzaldehyde 4 by the Reformatsky reaction [4]. The keto ester 6 was heated with ethylene glycol containing a small amount of p-toluenesulfonic acid in benzene to give the ketal 7 in 73% yield. Diisobutylaluminium hydride reduction of 7 afforded the aldehyde 8 in 78% yield.

1,2‐Diastereoselective C–C Bond‐Forming Reactions for the Synthesis of Chiral β‐Branched α‐Amino Acids

“…Strikingly, isomer E (18) shows a profile virtually identical to that of the N-Boc derivative with an anti/syn ratio of 85:15 and a regioselectivity of 95:5. However, for the Z isomer (19), the allylic substitution reaction was completely non-selective both regio-and diastereoselectively (entry 2). From this result it would appear that the N-Boc group plays an essential role during the allylic substitution of the Z-oDPPB ester 9.…”

“…[18] The mixture of diastereomers was reduced with lithium aluminium hydride and acetonide formation with 2,2-dimethoxypropane gave 36 in the same diastereomeric ratio thereby enabling the relative assignment of both syn and anti adducts (Scheme 3). [19] Scheme 3. Correlation of the relative stereochemistry of the dioxolane derivatives.…”

Hyperolactone C: Determination of its absolute configuration by comparison of experimental and calculated CD spectra

“…This native low shrub frequently occurs on sandy or eroding granitic soils in dry woods and pinelands, particularly in the Appalachian Mountain region of the southeastern United States. 3 The lactone ring contains two chiral carbon atoms (C 5 and C 9 ; for atom numbering, see Scheme 1), leading to two pairs of enantiomers ((5R,9R),(5S,9S) and (5R,9S),(5S,9R)) for hyperolactones B, C, and D. Total synthesis from chiral precursors established the absolute configuration of 3 as (5S,9S) 4 and that of hyperolactone B as (5R,9S). 5 As an alternative to total synthesis and/or X-ray crystallography of suitable diastereomeric derivatives, determination of the absolute configuration of chiral compounds by comparison of measured CD spectra with those obtained by quantum chemical calculations has become increasingly important.…”

Chemoselective and Regiospecific Synthesis of Iminospiro‐γ‐lactones from Maleic Anhydride or Citraconic Anhydride and Alkyl Isocyanides with Dialkyl Acetylenedicarboxylates

“…The unique structural nature of these spirocyclic compounds has attracted the interest of many synthetic organic chemists [13] [14]. The lactone moiety is also present in many natural products, especially insect pheromones, antifungal substances, and flavor components that occur in the essential oils of plants.…”