30094-28-1

Polyketide synthase (PKS) enzymes continue to hold great promise as synthetic biology platforms for the production of novel therapeutic agents, biofuels, and commodity chemicals. Dehydratase (DH) catalytic domains play an important role during polyketide

A synthesis of jolkinolide E from the bicyclic enone 3 using intramolecular Wittig reaction is described.In this synthesis a facile esterification method by means of a mixed anhydride of trichloroacetic acid catalized by DMAP, which culminates in the effective synthesis of the α,β,γ-trisubstituted butenolide ring, is also described.

(Chemical Equation Presented) A modular total synthesis of the potent V-ATPase inhibitors archazolid A and B is reported. The convergent preparation was accomplished by late-stage diversification of joint intermediates. Key synthetic steps involve asymmetric boron-mediated aldol reactions, two consecutive Still-Gennari olefinations to set the characteristic (Z,Z)-diene system, a Brown crotyboration, and a diastereo-selective aldol condensation of highly elaborate intermediates. For macrocyclization, both an HWE reaction and a Heck coupling were successfully employed to close the 24-membered macrolactone. During the synthetic campaign, a generally useful protocol for an E-selective Heck reaction of nonactivated alkenes and a method for the direct nucleophilic displacement of the Abiko-Masamune auxiliary with sterically hindered nucleophiles were developed. The expedient and flexible strategy will enable further SAR studies of the archazolids and more detailed evaluations of target-inhibitor interactions. 2009 American Chemical Society.

(Chemical Equation Presented) β-Aryl-β-ketophosphonates can be efficiently prepared in good yield by using a TFAA/85% H3PO 4-mediated acylation of electron-rich arenes with phosphonoacetic acids. The conditions offer advantages over

2-Quinolones are prepared from o-aminophenylketones by N-acylation with phosphonoalkanoylchlorides, followed by an intramolecular Horner-Wadsworth-Emmons olefination. The transformation proceeds under mild conditions, is generally applicable, gives good yields and can be performed either in two steps or as a one-pot reaction.

The archazolids are complex polyketides isolated from the myxobacterium Archangium gephyra and are potent inhibitors of vacuolar type ATPases. Herein, we report the first total synthesis of archazolid A, which establishes unequivocally the relative and ab

An efficient synthesis of (-)-mintlactone has been described starting from (+)-pulegone and employing the intramolecular Wittig-Horner reaction as the key step.

A variety of diethyl 1-substituted vinylphosphonates 8 has been conveniently synthesized by piperidine catalyzed decarboxylative condensation of 2-diethoxyphosphorylalkanoic acids and 2-diethoxyphosphorylalkenoic acids 7 with formaldehyde.

An enantioselective total synthesis of (-)-chlorothricolide (1) has been completed via a route involving the tandem inter- and intramolecular Dieis-Alder (IMDA) reaction of hexaenoate 19 and the chiral dienophile (R)-12. This reaction, which establishes s

Jolkinolide A, B, and E were efficiently synthesized from 9-methoxycarbonyl-4,4,10-trimethyl-Δ6-8-octalone 8 through Δ8(14)-podocalpen-13-one 12.A new synthetic method of γ-ylidenbutenolide consisting of mild esterification and the s

An efficient and general method for the preparation of 2-oxoalkane phosphonates 2 is described.Diethylphosphono-2-alkanoyl chlorides are used to introduce directly the 2-oxophosphonate 1-substituted synthons on Grignard or cuprate reagents.

Sequential treatment of a 2-halo carboxylic acid with a dialkyl phosphite and an aldehyde or ketone in the presence of 3 equiv of sodium hydride in glyme constitutes a new general acrylic acid synthesis superior to conventional methods.An alkoxide-in-alcohol variant may be used with bromo- or chloroacetic acid and aryl aldehydes to produce cinnamic acids conveniently.The scope and other features of the synthesis are discussed.

Process for preparing the substituted phosphonoalkanoic acid of the formula STR1 wherein: R1 is alkyl of 1-8 carbon atoms, aralkyl of 7-10 carbon atoms, phenyl, or substituted phenyl of 6-10 carbon atoms; R2 is H, hydrocarbyl of 1-18 carbon atoms, or substituted hydrocarbyl of 1-18 carbon atoms, wherein in said hydrocarbyl groups the carbon atom attached to the STR2 moiety is substituted with two or three hydrogen atoms or is a carbon atom of an aromatic ring; and Y is oxygen or sulfur, which process comprises contacting and reacting, at a temperature of about -70° C. to about 125° C., a pressure of about 1-100 atmospheres (0.1-10 MPa), and for a time sufficient to effect reaction, the phosphite ester of the formula STR3 wherein R1 and Y are as defined above, with the α-halocarboxylic acid of the formula R2 CHXCO2 H, wherein X is Cl, Br, or I and R2 is as defined above, in the presence of at least two moles of base per mole of limiting reagent, said base having a pKa greater than about 15, to produce the substituted phosphonoalkanoic acid, and process for preparing the substituted acrylic acid of the formula R3 R4 C=CR2 COOH wherein: R2 is as defined above; and R3 and R4 are the same or different and are selected from H, hydrocarbyl of 1-18 carbon atoms, and substituted hydrocarbyl of 1-18 carbon atoms or R3 and R4 taken together are cycloalkylene or substituted cycloalkylene of 4-18 carbon atoms, which process comprises: (a) carrying out the aforesaid reaction to produce the substituted phosphonoalkanoic acid except that at least three moles of base are present; and (b) contacting and reacting, at a temperature of about -70° to about 125° C., a pressure of about 1-100 atmospheres (0.1-10 MPa), and for a time sufficient to effect reaction, the substituted phosphonoalkanoic acid produced in step (a) with the carbonyl compound of the formula R3 R4 C=O, wherein R3 and R4 are as defined above, to produce the substituted acrylic acid.