Of -eremantholide

Carbocyclization of a radical derived from butyrolactone 91 onto an alkyne under reductive conditions gave the bicyclic lactone 92 in moderate yield [95JOC8179]. This intermediate was used m the total synthesis of (+)-eremantholide A 93. 

In 1991 Boeckman and co-workers reported the total synthesis of (+)-eremantholide A (8), as the natural enantiomer [28]. For construction of... 

In 1995 we accomplished the total synthesis of (+)-eremantholide A (8). Our synthetic scheme was completely different from that of the Boeckman group. We selected our building block 2 as the starting material, and the retrosynthetic analysis is outlined in Scheme 6. At first, disconnection of two carbon-carbon bonds in 8 as depicted leads to two fragments, an A/B ring equivalent 55 and known disubstituted 3(2if)-furanone derivative 56. We planned the direct connection of intact 3(2if)-furanone 56 to 55 at a... 

Ramberg-Backlund rearrangement. The key step in a synthesis of (+)-eremantholide A (4), involves ring contraction of the chloro sulfone 2 by the Ramberg-Backlund rearrangement. Thus treatment of 2 with this highly hindered base (1), 2.2 equiv., and HMPA (10 equiv.) in DME at 70° provides 3 in 82% yield. Use of less hindered bases results mainly in reduction of the chloro group. 

A similar double substitution in a single pot was employed for thioether formation in the RBR-based synthesis of eremantholide A (see Section 8.6.41. " In this case, the sulfide generated from hexamethyldisilathiane [bis(trimethylsilyl)sulfide] and sodium methoxide reacted with the bromoiodide 16 to form the 10-membered thioether 17 (Scheme 8.6). This was oxidized with Oxone to provide the sulfone 18. 

The isolation and structural studies of more than 500 ses-quiterpenoids have been reviewed in 2009. These compounds act as alarm pheromone ( , )-a-famesene), as antifeedants (cinnamadin, (5)-(+)-curcuphenol), and show antibacterial (bisabolane derivatives) and antitumor properties. NMR spectroscopy was widely used for the characterization of their stereochemistry. An analysis of the and C NMR spectra of eremantholide C (Figure 49.8) and its analogs was described. ... 

FIGURE 49.8. Structures of eremantholide C, roridin A, verrucarin A, gorgonolide, ludartin, artemisin, and (+)-taxifolin. 

Synthetic studies on sesquiterpenoids from D-glucose, total syntheses of (-H)-eremantholide A and (—)-verrucarol 98YGK1026. 

The crystal structure of 18-hydroxydecipia-2(4),14-dien-l-oic acid (98) has been published. The structure and absolute stereochemistry of a novel tetracyclic diterpenoid, stemarin (99), has been described. Eremantholide A(IOO) is a tumour-inhibitory compound which has been obtained from Eremanthus eleagnus (Compositae) and is possibly a nor-diterpenoid. The structure of colletotrichin (formerly known as acetylcolletotrichin) (101), which has been determined by an... 

A number of oxacyclic natural products were synthesized via carbocycle-forming radical reaction of oxacyclic intermediates. An early example is the synthesis of (-)-dihydroagarofuran (170) by Biichi [109] (Scheme 58). The bridgehead chloride 168 obtained from the corresponding hydroxy ketone was amenable to radical cycliza-tion, and the tricyclic ether 169 was duly obtained. The aplysin synthesis [110] provides another example, and (—)-karahana ether (173) was synthesized via radical cyclization of the substrate 171 [111] (Scheme 59). Lactonic natural products (-1-)-eremantholide A [112], alliacolide [113], and (-)-anastrephin [114] were prepared via a variety of carbocycle-forming radical cyclization reactions. In the total synthesis of spongian-16-one (176) [115] (Scheme 60), the butenolide moiety in the substrate 174 served as the final radical acceptor for three consecutive 6-endo-. rig cyclizations. 

Eremantholide A (74), a member of the fiiranoheliangolides, has been synthesized in 21 steps starting from 56 [24]. The early part of the synthesis is outlined in Scheme 11. Alkylation of 56 with 2,3-dibromopropene affords the (2 S, 4/ )-dioxolanone 70 (> 98% de) and reaction with Tebbe reagent produces 71. The bromide is converted to a mixed cuprate, and the organometallic is added in a 1,4-fashion to butenolide 72, which is derived from D-mannitol. 

In this article, we detail our novel total syntheses of two biologically and structurally intriguing sesquiterpenes, (+)-eremantholide A (8) [18] and (-)-verrucarol (9) [19] (Fig. (2)). These syntheses again commenced with the Claisen rearrangement product 2. In addition, previous reports concerning the synthetic efforts for these two natural products from other groups are briefly introduced. 

In the initial period of our synthetic efforts on the construction of the A/B ring equivalents, we had prepared two functionalized tetrahydrofuran-3-ones 62 and 64 from 2 (Scheme 7). We experienced at that time much difficulty in the C7-C8 bond formation (the eremantholide numbering) by means of an intramolecular aldol (62 to 63) or an intramolecular Horner-Emmons (64 to 65) reaction. After throughout investigations examined using theses and related substrates, we finally abandoned the A/B ring construction by means of these base-mediated "polar" carbon-carbon bond forming reactions. 

In a study on the biosynthesis of the polyether antibiotic lasalocid A, a syn-selective Evans aldol reaction of 83 with methacrolein gave 84 in 95% isolated yield. In the total synthesis of the antitumor sesquiterpenoid (+)-eremantholide A, an Evans aldol reaction was used to deliver a single syn-... 

The fused cyclopentane 25 has been prepared by radical cyclization via deoxygenation of 24 (Scheme 4). This ring system is a carbocyclic analogue related to the A/B ring system of the cytotoxic sesquiterpene, (+)-eremantholide. 

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