Of sarcophytol

Up to 20 sarcophytols were isolated from the Sarcophyton genus with the name of sarcophytol from A to T (except sarcophytol L, including two sarcophytol T) (Figure 6-2). 

Chemical examination of Sarcophyton glaucum collected at Ishigaki island, Okinawa Prefecture, resulted in the isolation of seven cembranoid diterpenes, namely sarcophytol A (3), sarcophytol A acetate (4), sarcophytol B (5), sarcophy-tonin A (6), and minor constituents sarcophytol C (7), D (8), and E (9). These compounds were found to be susceptible to autooxidation while being purified. The structural determination of these compounds was made mainly based on proton and carbon nuclear magnetic resonance (NMR) spectral evidence and degradative studies by ozonolysis. X-ray crystallographic analysis for the two crystalline compounds, sarcophytol B (5) and D (8), has been reported. The total lipid extracts of S. glaucum comprise about 40% sarcophytol A (3), 5% each of sarcophytol A acetate (4) and sarcophytonin A (6), about 1% sarcophytol B (5), and minor amounts of sarcophytol C (7), D (8), and E (9). 

The first total synthesis of sarcophytol A (3), which was reported by Takayanagi et al. in 1990, ° was achieved in a highly stereo- and enantioselective manner starting from , -famesol (91) it included (1) a newly developed Z-selective (Z > 35 1) Horner-Emmons reaction with a phosphonate nitrile, (2) modified cyanohydrin macrocyclization, and (3) enantioselective (93% ee) reduction of macrocyclic ketone 100 as its key steps (Scheme 6-1). 

Then Li et al. reported on a concise total synthesis of ( )-sarcophytol A (3) from the derivative of , -farnesol (91) by a low-valent titanium-mediated intramolecular McMurry olefination strategy (Scheme 6-4). ... 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

The closure of the macrocyclic ring by means of an intramolecular 8 2 reaction is a straightforward approach, and sulfur-stabilized carbanion alkylation has been successfully applied in the synthesis of 14-membered cembranoids. The synthesis of nephthenol (40) and cembrene A (59) is an example of this methodology. In Li and Yue s report, the total synthesis of ( )-sarcophytol M (17) was achieved from ger-aniol (137) through 12 steps and in 8.9% overall yield with an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as a key step. This example is the first of the closure of a macrocyclic ring with the intramolecular nucleophihc addition of a sulfur-stabilized carbanion to a ketone (Scheme 6-7). 

Kodama, M., Yoshio, S., Yamaguchi, S., Fukuyama, Y., Takayanagi, H., Morinaka, Y., Usui, S., Fukazawa, Y. Total syntheses of both enantiomers of sarcophytols A and T based on stereospecific [2,3]Wittig rearrangement. Tetrahedron Lett. 1993, 34, 8453-8456. 

Sarcophytol B. McMurry has utilized a diastereoselective pinacol cyclization of a 1,14-dialdehyde in the final step of a five-step synthesis of sarcophytol B, a cem-brane sesquiterpene (Eq. 3.8) [25]. This work established the relative stereochemistry of the natural product [26]. 

Takayanagi, H., Sugiyama, S., and Morinaka, Y., A ketal Claisen rearrangement for a-ketol isoprene unit elongation. Application to a practical synthesis of sarcophytol A intermediate, J. Chem. Soc., Perkin Trans. 1, 751, 1995. 

Scheme 3. Proposed biogenesis of Sarcophytol A from Cembrene by oxidation.

Koh, M., Iwanaga, T, Hatanaka, M., Nakano, A., Morihara, K., and Takemura, K. (2000) Distribution of sarcophytol A in soft coral of the Sarcophyton genus. Bioscl Biotechnol. Biochem., 64, 858-861. 

Takayanagi, H., Kitano, Y, and Morinaka, Y. (1994) Total synthesis of sarcophytol A, an anticarcinogenic marine cembranoid. /. Org. Chem, 59,2700-2706. 

Takashi, T, Yokoyama, H., Haino, T, and Yamada, H. (1992) Enolate reactions on macrocydic ring systems total synthesis of ( )-sarcophytol A./. Org. Chem., 57, 3521-3523. 

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