144754-24-5

Pavettamine, a plant toxin first isolated from Pavetta harborii in 1995, was previously identified as a polyamine with C2 symmetry and a 1,3-syn-diol moiety on a C10 carbon backbone – one of very few substituted polyamines to be isolated from nature. Its absolute configuration was later established by our first reported total synthesis in 2010. Herein we report the first total synthesis of the enantiomer of pavettamine, ent-pavettamine. The symmetrical structure of the molecule allows for the synthesis of a common C5 fragment that can be divergently transformed into two synthons for later convergent coupling to furnish the target carbon framework. Based on the success of the protocol we employed for the synthesis of the naturally occurring pavettamine, (S)-malic acid was again the starting material of choice for the synthesis of the two individual C5 fragments, with strategic differences in terminal-group manipulation allowing for the synthesis of ent-pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine functional groups as they were unveiled. The functionalized C5 fragments were coupled via reductive amination revealing the C10 carbon backbone. Deprotection of the alcohol and amine functional groups successfully provided ent-pavettamine as a TFA salt.

The first total synthesis of (-)-marinisporolide C is described, which establishes unequivocally the relative and absolute configuration of this oxopolyene macrolide. Key features of this synthesis include a series of highly stereoselective aldol reactions followed by directed reductions to build the polyol domain, a Stille cross-coupling reaction to assemble the polyene, and an intramolecular Horner-Wadsworth-Emmons olefination to forge the macrocyclic ring. Despite the initial approach to marinisporolide A using a Yamaguchi macrolactonization reaction that was unsuccessful due to steric hindrance of the oxygen at the C33 position, we were able to prepare a known derivative of marinisporolide A and consequently confirm its stereochemical assignment.

The first total synthesis of (-)-marinisporolide C was performed in 25 steps (longest linear sequence) and an overall yield of 1%. Due to the high degree of convergence and robustness, the C9-C35 fragment that corresponds to the polyol portion was obtaine

(Chemical Equation Presented) Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (75) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C22 oxylipins that parallels a hypothesis put forward previously to explain the origin of C20 cyclopropane-containing algal products.

Asymmetrie total syntheses of solandelactones E and F confirmed that hydroxyl configuration at C11 in these oxylipins had been misassigned and that the stereochemistry at this center should be reversed. Key steps in the synthesis involved a Nagao asymmetr

The present invention relates to optically active boronate derivatives which are useful as intermediates for the synthesis of HMG-CoA enzyme inhibitors such as atorvastatin, cerivastatin, rosuvastatin, pitavastatin, and fluvastatin.

Marine oxylipin bacillariolides I-III were synthesized from (R)-malic acid, using diastereoselective one-pot formation of the chiral cyclopentane derivative from the anion of allyl phenyl sulfone and chiral epoxymesylate as the key reaction. (C) 2000 Elsevier Science Ltd.

Practical syntheses of the C9-C14 sterotriade 5 and the C1-C8 polyene unit 6 in ansatrienine A (mycotriene) (1a), and other ansamycin antibiotics is described. A key step for controlling the configuration of the stereogenic center at C13 involves the stereoselective reduction of enone 10 using the Evans-Tishchenko reaction.

The marine antibiotic korormicin, isolated from the culture filtrate of marine bacterial strain Pseudoalteromonas sp. F-420, specifically inhibits the growth of marine Gram-negative bacteria without affecting terrestrial species. The absolute configuration of korormicin was determined by the combination of a CD exciton chirality method and chemical degradation. Convergent total synthesis of korormicin has been also achieved.

Marine eicosanoid bacillariolide II was synthesized from (R)-malic acid, involving the diastereoselective one-pot formation of chiral cyclopentane derivative 12 from the anion of allyl phenyl sulfone and chiral epoxymesylate 11 as the key step.

A new efficient entry into cis monobactams starting from β-hydroxyesters is reported.This preparation is based on the stereoselective "electrophilic amination" of β-hydroxyester dianions and on Miller's biomimetic synthesis of the β-lactam nucleus.By this route, key intermediates for the preparation of pharmacologically important cis aztreonam 2 and carumonam 3 were prepared.

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The syntheses of chiral synthones 13-16 are described utilizing the chiral pool approach starting from either S- or R-malic acid.

Compounds of formula I wherein R1, R2, Q, X and Y have various significances,in free acid form, or in the form of an ester or δ-lactone thereof, or in salt form as appropriate, are described. They are indicated for use as hypolipoproteinemic and anti-athe

Process for the synthesis of compounds of the formula STR1 in R[R*,S*] enantiomeric form, wherein each P1 is independently an hydroxy group-protecting group, and R2z is C1-4 alkyl, benzyl or allyl, comprising, as a key step when R2z is R2x, the reaction of the compound of the formula STR2 in (S) enantiomeric form with a compound of the formula to obtain a compound of the formula STR3 in (S) enantiomeric form, and, as a key step when R2z is R2y, the reaction of a compound of the formula STR4 in (S) enantioimeric form with a compound of the formula to obtain a compound of the formula STR5 in (S) enantiomeric form, wherein R2x is primary or secondary C1-4 alkyl, benzyl or allyl, R2y is C1-4 alkyl not containing an asymmetric carbon atom, and R3 ' is methyl or ethyl, processes for the synthesis of compounds of the formula STR6 comprising reacting a compound of the formula STR7 with the reaction product of a strong base and a compound of the formula STR8 optionally followed by, when R2z is allyl, cleavage of the allyl and P1 groups to obtain the corresponding compound of the formula STR9 wherein each R7 is methyl or ethyl, R is as defined in the specification, and each P1 independently and R2z are as defined above, and the compounds of the formula STR10 wherein R and each R7 are as defined above.