Marine diterpene

Provided that the silanolate elimination proceeds with anti selectivity, it must be concluded, that the intermediate homoallylic alcohol has an anti configuration, and thus the reagent has an ( -configuration. Acidic hydrolysis of the enol ether leads to enones the overall sequence consists of a nucleophilic acroylation. This has also been applied in the total synthesis of the marine diterpene ( )-aplysin-2067. 

In the course of dolastane synthesis (the dolastanes are a group of marine diterpenes) interesting rearrangements catalyzed by Lewis acids were found. Treatment of the trienone 293 with excess (1.5 eq) ethylaluminum dichloride at low temperatures (—5°C, 48 h) gave the tetracyclic enone 295 in 53% yield while the tricyclic dienone 296 (50%) was formed at room temperature (equation 102)156. It was assumed that both products can be derived from the common zwitterion 294 which undergoes intramolecular alkylation at low temperatures (path a) whereas an alkyl shift takes place at elevated temperatures (path b), followed by a 1,2-hydride shift (equation 102). 

In contrast to the small number of known halogenated (chlorinated) terrestrial diterpenes (vide supra), the number of marine diterpenes is very large, and more than 130 were documented in the initial survey (7). 

Ohtani, I., Kusumi, T., Ishitsuka, M. O., and Kasikawa, H. 1989. Absolute configuration of marine diterpenes possessing a xenicane skeleton. An application of an advanced Mosher s method. Tetrahedron Lett. 30, 3147-3150... 

The wide-ranging biological activities exhibited by members of the cembranoid family of marine diterpenes, for example, deoxysarcophine, lophotoxin, sinularin, aseperdiol, and sarcophytol A, in combination with their diversity of structure and the lack of flexible synthetic methodology for the elaboration of 14-ring carbo-cycles, have made this family of natural products a particularly challenging area for the synthetic chemist. Methods that have been developed for macrocyclization in the cembranoid field include... 

Other complementary methodologies include the preparation of substituted cyclopropanes from glycals using rhodium acetate carbenoid additions [65,66]. Additionally, acid catalyzed cyclopropane opening reactions in alcoholic solutions afford the 2-C-branched-glycosides. These combined reactions were used to prepare a key intermediate in marine diterpene norrisolide synthesis from D-mannose [67]. 

Synthesis of (+)-Chatancin. The alkylation of an a-sulfonyl carbanion derived from a y-alkoxy functionalized sulfone with an allylic bromide and subsequent reductive desulfonylation with Na/Hg constitutes a key step in the synthesis of the marine diterpene (+)-chatancin (Eq. 144).251... 

A group of challenging target molecules with important biological activities are the pseudopterosins [23] and the seco-pseudopterosins [24], marine diterpene glycosides with strong anti-inflammatory properties (Fig. 3). 

The helioporins, a group of marine diterpenes with antiviral and cytotoxic properties, are structurally closely related to the (seco-) pseudopterosins and all possess a characteristic benzodioxole unit [29]. Their stereostructure was assigned as shown in Fig. 4 with a cfs-relationship of the two benzylic sidechains at the tetralin nucleus. 

Kusani, T., T. Hamada, M.O. Ishitsuka, I. Ohtani, and H. Kakisawa Elucidation of the Relative and Absolute Stereochemistry of Lobatriene, a Marine Diterpene, by a Modified Mosher s Method. J. Organ. Chem. (USA), 57, 1033 (1992). 

A synthesis of the marine diterpene geranyllinaloisocyanide 1652 has been successfully accomplished by a novel regioselective allylamine construction, which is achieved by an allyl cyanate-to-isocyanate rearrangement 1649 —> 1650. The resulting formamide 1651 is dehydrated with triphenylphosphane/tetrabromomethane to give the geranyllinaloisocyanide 1652 in 82% yield [1226]. 

Williams DR, Coleman PJ, Henry SS. Synthesis strategies for marine diterpenes. Total synthesis of the clavularanes. / Am. Chem. Soc. 1993 115 11654 11655. 

Hiroto, N. (1989) Total synthesis of a marine diterpene, sanadaol. J. Synth. Org. Chem. Japan, 47, 224-232. 

Mischne, M.P., Sierra, M.G., and Ruveda, E.A. (1984) Synthesis of novel marine diterpenes epiisocopalenedial, isocopalenedial, acetoxyisocopalenal from methyl isocopalate. J. Org. Chem., 49, 2035-2037. 

Kusumi, T, Hamada, T., Ishitsuka, M.O., Ohtani, 1., and Kakisawa, H. (1992) Elucidation of the relative and absolute stereochemistry of lobatriene, a marine diterpene, by a modified Mosher method. J. Org. Chem., 57,1033-1035. 

Rodriguez, A.D. and Ramirez, C. (2000) A marine diterpene with a novel tetracyclic framework from the West Indian gorgonian octocoral Pseudopterogorgia disabethae. Org. Lett., 2, 507-510. 

Rodriguez, A.D. and Shi, Y.P. (2000c) Verriline a highly oxygenated marine diterpene based on the novel verrilane carbon skeleton. /. Org. Chem., 65, 5839-5842. 

Nowakowski, M. and Hoffrnaim, H.M.R. (1997) Synthesis of bridged nine-membered ring ethers studies directed towards the synthesis of eimiceDin-based marine diterpenes. Tetrahedron, 53, 4331-4338. 

Iwashima, M., Nagaoka, H., Kobayashi, K., and Yamada, Y. (1992) Total synthesis of marine diterpene fuscol. Tetrahedron Lett., 33, 81-82. 

Mehta, G. and Kumaran, R.S. (2001) Studies towards the total synthesis of novel marine diterpene havellockate constmction of the tetracyclic core. Tetrahedron Lett., 42, 8097-8100. 

Horstermarm, D., Schmalz, H.-G., and Kodok-Kohii, G. (1999) Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)3 chemistry. Tetrahedron, 55,6905-6916. 

Greene, A.E., Highly stereoselective total syntheses of (+)-pachydictyol A and (-)-dictyolene, novel marine diterpenes from brown seaweeds of the family dictyotaceae, /. Am. Chem. Soc., 102, 5337, 1980. 

---