Applications to Total Synthesis

More recently, the first total synthesis of (-h)-brasilenyne, an antifeedant isolated from the sea hare Aplysia hrasiliana) by Fenical in 1979 [83], was reported [84]. This report makes novel use of the cyclic silyl-ether-generating RCM/cross-coupUng sequence. The synthesis of (-l-)-brasilenyne is achieved from L-malic acid in 19 steps 

The numerous methods for stereoselective epoxide synthesis and the extensive base of knowledge regarding regiocontrol in intramolecular opening reactions combine to create numerous opportunities for natural product synthesis. This section will illustrate many of the routes that have exploited this approach. These routes are often called biomimetic syntheses due to 

SCHEME 4.29 Morimoto s total synthesis of longilene peroxide. 

Morimoto reported the synthesis of omaezakianol through propose that acid-mediated hydrolysis occurs at the dimethyl 

SCHEME 4.32 Epoxide hydrolase mimiery for the synthesis of omaezakianol. 

33% yield. Hydrolysis at the opposite terminus would yield the enantiomer of the natural product, so the observation of high enantiocontrol for product formation supports the authors mechanistic hypothesis although the reason for the selectivity is not clear. 

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Subsequent examination of a tethered alkyne-VCP with rhodium(i) resulted in the first metal-catalyzed [5 + 2]-reaction. Excellent yields were obtained with a variety of substrates (Scheme 3) irrespective of the steric and electronic nature of the R1 group. Notably, quaternary centers are accessed in high yield. Since this first report, in-depth studies on catalysts, substrate scope, selectivity, and applications to total synthesis have been carried out. Work in this area has been reviewed.23-26... 

The metal-catalyzed [5 + 2]-cycloaddition reaction of VCPs and 7t-systems provides a new concept for seven-membered ring construction that has been significantly advanced over the last decade in the areas of catalyst development, chemo-, diastereo-, and enantioselectivity, substrate scope, and applications to total synthesis. 

Iwasawa, N. Funahashi, M. Hayakawa, S. Ikeno, T. Narasaka, K. Synthesis of mediumsized bicyclic compounds by intramolecular cyclization of cyclic /i-keto radicals generated from cyclopropanols using Mn(III) tris(pyri-dine-2-carboxylate) and its application to total synthesis of 10-isothiocyanatoguaia-6-ene. 

Heathcock, C.H., Finkelstein, B.L., Jarvi, E.T., Radel, PA. and Hadley, C.R. (1988). 1,4-and 1,5-Stereoselection by sequential Aldol addition to a,6-unstaurated aldehydes followed by Claisen rearrangement. Application to total synthesis of the vitamin E side chain and the archaebacterial C40 diol. J. Org. Chem., 53,1922-1942. 

Ishikawa T, Shimizu Y, Kudoh T, Saito S (2003) Conversion of D-glucose to cychtol with hydroxymethyl substituent via intramolecular silyl nitronate cycloaddition reaction application to total synthesis of (+)-cyclophelhtol. Org Lett 5 3879-3882... 

In this chapter, we first summarize more or less basic works on the synthesis of the common and basic skeletons of various types of natural alkaloids, aiming at their application to total synthesis, and also those works that seem applicable to the above syntheses, and then collected works on total syntheses of alkaloids via the route involving enamide cyclization. 

Numerous applications to total synthesis of natural products have been reported. In the case of the macrolide (i )-lasiodiplodin, the achiral ester (eq 5) was reacted with the (+)-(i )-methyl p-tolyl sulfoxide derived anion to give the corresponding p-keto sulfoxide, which was then reduced with DIBAL to give, after desulfurization, the seco-ester of (i )-lasiodiplodin (eq 5). This is an example showing that the chirality can be introduced at the end of the synthesis in the desired configuration. 

Marsault, E., Toro, A., Nowak, P., Deslongchamps, P. The transannular Diels-Alder strategy applications to total synthesis. Tetrahedron 2001,57,4243 260. 

Ishikawa, T., Shimizu, Y., Kudoh, T., Saito, S. Conversion of D-Glucose to Cyclitol with Hydroxymethyl Substituent via Intramolecular Siiyi Nitronate Cycloaddition Reaction Application to Total Synthesis of (+)-Cyclophellitol. Org. Lett. 2003, 5, 3879-3882. 

Bach, T. The Patemo-Buchi reaction of N-acyl enamines and aldehydes - the development of a new synthetic method and its application to total synthesis and molecular recognition studies. SynlettZOOO, 1699-1707. 

Hu, T., Takenaka, N., Panek, J. S. Asymmetric Crotylation Reactions in Synthesis of Polypropionate-Derived Macrolides Application to Total Synthesis of Oleandolide. J. Am. Chem. Soc. 2002,124,12806-12815. 

Since the monumental accomplishments of Woodward s total syntheses of strychnine in 1954 [I] and rcserpinc in 1958 (2], the arsenal of synthetic methods in indole alkaloid synthesis has greatly expanded. In the same time period, the use of palladium chemistry in organic syntheses has also witnessed tremcndou- growth with an ever-expanding repc loire of synthetic methods and their applications to total synthesis. The use of palladium chemistry for the synthesis of indole alkaloids has been explored, and several examples have been included in recent reviews [3-6]. This account attempts to present a comprehensive collection of total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. 

The Transannular Diels-Alder Strategy Application To Total Synthesis," Marsault, D. Tor6, A. Nowak, P. Deslongchamps. P. Tetrahedron, 2001, 57, 4243. 

Ishizaki M, Hoshino O (2003) Pauson-Khand reaction of enynes bearing exo-olefin and its application to total synthesis of Lycopodium alkaloid, magellanine. J Synth Org Chem Jpn 61 1166-1175... 

Reding MT, Kaburagi Y, Toknyama H, Fukuyama T (2002) Synthesis of 2, 3-disubstituted indoles by radical cyclizatiott with hypophosphorous acid and its application to total synthesis of ( )-catharanthine. Heterocycles 56 313—330... 

Suzuki Y, Murata T et al (2002) The intramolecular Diels-Alder strategy applications to total synthesis of natural products. Yuki Gosei Kagaku Kyokaishi 60 679-690... 

Tethered aminohydroxylation reaction and its application to total synthesis 12EJ0655. 

In summary, the DBR is a powerful method for the construction of highly substituted phenols, quinones, and heterocycles. Signifieant effort has gone into exploring the scope of the reaction since its initial discovery. This exploration has enabled the confident predietion of regiochemistry and the application to total synthesis. Further efforts to predict and control stereochemistry are needed to inerease the utility of this valuable reaction. 

For a detailed review on Prins/ pinacol reaction and its application to total synthesis of complex natural products. Overman, L.E.,... 

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