Marine macrolide

Scheme 40 (E)-Selective macrocyclization in the total synthesis of the marine macrolides dactylolide (202) and zampanolide (203) [99]...

In Ghosh s enantioselective total synthesis of the cytotoxic marine macrolide (+)-amphidinolide T1 (318) [143], the C1-C10 fragment 317 was constructed by CM of subunits 315 and 316 (Scheme 62). The reaction mediated by catalyst C (5 mol%) afforded in the first cycle an inconsequential 1 1 mixture of (E/Z)-isomeric CM products 317 in 60% yield, along with the homodimers of 315 and 316. The self-coupling products were separated by chromatography and exposed to a second metathesis reaction to provide olefins 317 in additional 36% yield [144]. 

Scheme 62 Efficient coupling of fragments 315 and 316 via CM in Ghosh s total synthesis of the cytotoxic marine macrolide amphidinolide T1 (318) [143]...

The marine macrolides latrunculin A and the less potent variation latrunculin B (5-25 pg/mL, 60 minutes) bind to actin and disrupt the cytoskeleton at low concentrations (90,91). Their mechanism of action includes binding to and sequestering actin monomers, resulting in filament depolymerization (89). 

Spector I, Shochet NR, Blasberger D, Kashman Y. Latrunculins—novel marine macrolides that disrupt microfilament and affect cell growth L Comparison with cytochalasin D. Cell Motil Cytoskeleton 1989 13 127-144. 

The first total synthesis of the marine macrolide leucascandrolide A relied upon the use of two key hydroformylahon reactions [25]. Yb(OTf)3-catalyzed oxymercuration of homoallylic alcohol 46 provided organomercurial 47, which was hydroformylated to give... 

Other procedures using TPAP/NMO/PMS/CH Cl include steps in the synthesis of (+)-altholactone (lactol to lactone) [78] antheliolide A [168] the AChE inhibitor (+)-arisugacin A and B (primary alcohol to aldehyde step also) [83] the marine macrolide amphidinolide T1 [169] the alkaloid (+)-batzelladine D cf. mech. 

Hoye described an RCM-based total synthesis of the 20-membered marine macrolide dactylolide 288 and its subsequent conversion to the natural carbinolamide zampanolide 289 (Scheme 56), both feature a common highly unsaturated macrolide core, bridging a m-2,6-disubstituted 4-methylene tetrahydropyran unit. When the polyunsaturated acyclic lactone 286 (1 1 epimeric mixture around the /i r/-butyldimethylsilyl (TBS)-protected carbinol center) was in situ protected with bis-trimethylsilylacetamide (BSA) and then treated with catalyst G in benzene at 60 °C, each diastereomer smoothly cyclized to the corresponding cycloalkene 287 with exclusive ( )-geometry at the newly formed double bond. 

We mentioned earlier the in vitro antimalarial activity of halichondramide and swin-holide A.22 The initial testing of compounds 3 to 5 displayed 75 to 100% mortality of both corn rootworm and tobacco budworm. On titration, they displayed an LCS0 range of 10 to 100 ppm, and induced 30, 85, and 30% corn rootworm larval stunting, respectively. Both halichondramide and swinholide A caused 85% tobacco budworm larval stunting. The significant insecticidal activity of these compounds (3 to 5) indicates that further QSAR studies of the compounds would be valuable. These compounds illustrate the necessity to examine various marine macrolides as potential prototype insecticides. 

This chapter attempts to recount some of the highs and lows encountered during the Paterson group s total synthesis of spongistatin 1/altohyrtin A, an extremely rare marine macrolide with a seductively complex structure in combination with displaying promising anticancer properties. We provide the reader with an emotional roller coaster ride through a project that spanned some 7 years, with early studies aimed at... 

Yeung K-S, Paterson I (2005) Advances in the Total Synthesis of Biologically Important Marine Macrolides. Chem Rev 105 4237... 

Pietruszka J (1998) Spongistatins, Cynachyrolides, or Altohyrtins Marine Macrolides in Cancer Therapy. Angew Chem hit Ed 37 2629... 

Paterson I, Findlay AD, Florence GJ (2007) Total Synthesis and Stereochemical Reassignment of (+)-Dolastatin 19, a Cytotoxic Marine Macrolide Isolated from Dolabella auricularia. Tetrahedron 63 5806... 

The samarium-catalyzed reduction was utilized in the asymmetric synthesis of the marine macrolide bryostatin 2 (42) to furnish an intermediate (46)12 (Scheme 4.21). The ketone 43 underwent an aldol reaction with the ketoaldehyde 44 via the isopinylboryl enolate to give the aldol adduct 45 in good yield and 93 7 diastereoselectivity. Subsequent samarium-catalyzed Evans-Tishchenko reduction of the (3-hydroxy ketone 45 provided the p-nilrobenzoale 46 with excellent stereoselectivity. Silylation and saponification readily converted compound 46 into the alcohol 47 in 88% yield over two steps. 

In the synthesis of the marine macrolide leucascandrolide A (54), Kozmin used the samarium-catalyzed diastereoselective ketone reduction method in a highly stereocontrolled synthesis of the C1-C15 fragment 5814 (Scheme 4.2n). Generation of the dicyclohexylboron enolate of the ketone 55 followed by addition... 

Developments in the chemistry of the smenochromenes, marine macrolides with a chromene core, include a four-step synthesis of racemic smenochromene D 16 from hydroxyfamesyl acetate and 4-hydroxy-3-methoxyphenyl formate and its conversion into racemic smenochromene B by way of a macroring contraction and bond isomerisation <07T6529>. Several [/>,c]-fuscd chromans, e.g. 17, related to rhododaurichromanic acid and... 

A Rh2(OAc)4-catalyzed cycloaddition between nitrile 202 and dimethyl diazomalonate 203 gave oxazole 204 which was further elaborated into the side-chain of marine macrolide leucascandrolide A (Scheme 59) <2002JA13670>. 

Strobel and co-workers isolated haterumalide NA/oocydin A (2) from bacteria Sermtia marcescens [10]. Haterumalide NA was also obtained from a soil bacterium [11]. The isolation of similar compounds from two unrelated invertebrates such as the ascidian Lissoclinum sp. and the sponge of Ircinia sp., and the microorganisms, supports the potential microbial origin of haterumalides [12-15]. Although more than 200 marine macrolides have been recorded since the first isolation of the aplysiatoxins, halogenated marine macrolides are rarely found [16, 17]. 

The stereoselective synthesis of the C5-C20 subunit of the aplyronine family of polyketide marine macrolides was accomplished by J.A. Marshall and co-workers. The C15-C20 moiety was prepared using the original Seyferth-Gilbert homologation conditions. The diazophosphonate was deprotonated with potassium fert-butoxide at low temperature, and then the solution of the aldehyde was added slowly also at low temperature. Interestingly, the alternative Corey-Fuchs alkyne synthesis was unsuccessful on this substrate, since extensive decomposition was observed. 

Bryostatins. The bryostatins are a group of cytotoxic marine macrolides, isolated from invertebrate filter feeders, that exhibit promising anticancer activity (Scheme 9-36). Two completed total syntheses of the bryostatins have demonstrated the versatility and power of aldol reactions in the concise assembly of complex polyketides. 

Stereoselective total syntheses of Zincophorin, the ionofore antibiotic (substituted tetrahydropyrane), and Scytophycin C, an antitumor marine macrolide 04YGK1080. 

Shibata N, Yamamoto T, Torn T (2007) Synthesis of Thalidomide. 8 73-97 Shindo M (2006) Total Synthesis of Marine Macrolides. 5 179-254 Solomon VR.see Prabhakar YS (2006) 4 161-248... 

Higa, T., and Tanaka, J. (1997). Bioactive marine macrolides. In Studies in Natural Products Chemistry (A. Rahman, Ed.), Vol. 19, pp. 549-626. Elsevier Science, Amsterdam. 

Pietruszka, J. (1998). Spongistatins, cynachyrolides, or altohyrtins Marine macrolides in cancer therapy. Angew. Chem. Int. Edit. Engl. 37, 2629-2635,... 

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