Harry H. Wasserman

Prodigiosins as a New Group of H+/Cl−Symporters That Uncouple Proton Translocators

We reported previously (Kataoka, T., Muroi, M., Ohkuma, S., Waritani, T., Magae, J., Takatsuki, A., Kondo, S., Yamasaki, M., and Nagai, K. (1995) FEBS Lett. 359, 53–59) that prodigiosin 25-C uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification, and affected glycoprotein processing. In the present study we show that prodigiosins (prodigiosin, metacycloprodigiosin, and prodigiosin 25-C) inhibit the acidification activity of H+-ATPase chloride dependently, but not membrane potential formation or ATP hydrolysis activity, and suggest that they promote H+/Cl− symport (or OH−/Cl− exchange, in its equivalence) across vesicular membranes. In fact, prodigiosins displayed H+/Cl− symport activity on liposomal membranes. First of all, they decreased the internal pH of liposomes depending on the external chloride, and raised it depending on the internal chloride when external buffer was free from chloride. Second, their effect was electroneutral and not seriously affected by the application of an inside positive membrane potential generated by K+ and valinomycin. Finally, they promoted the uptake of [36Cl] from external buffers with concomitant intraliposomal acidification when external pH was acidic relative to liposome interior. As prodigiosins hardly inhibit the catalytic activity (ATP hydrolysis) unlike well known OH−/Cl− exchangers (for example, tributyltin chloride), they should provide powerful tools for the study of molecular machinery and cellular activities involving transport of protons and/or chloride.

Transamidation reactions using β-lactams. The synthesis of homaline

Abstract The synthesis of the plant product, homaline, by a translactamization process involving the β-lactom, (−)-4-phenyl-2-azetidinone, is described.

The chemistry of vicinal tricarbonyls a total synthesis of prodigiosin

Abstract The addition of primary amines to alkenyl vicinal tricarbonyls leads to 5-substituted-3-hydroxypyrroles. This reaction has been employed in a synthesis of the 2-formyl-3-methoxy-α,α′-bipyrrole precursor of the prodigiosin family of natural products.

Activated carboxylates from the photooxygenation of oxazoles : Application to the synthesis of recifeiolide, curvularin and other macrolides

Abstract Oxazoles may be used as masked forms of activated carboxylic acids since they readily form triamides on reaction with singlet oxygen. With 2-alkyl-4,5-diphenyloxazoles, the triamides formed on photooxygenation undergo selective nucleophilic attack at the acyl carbonyl derived from the 2-oxazole position. Using 2-(ω- hydroxyalkyl)-4,5- diphenyloxazoles as substrates, the oxidation-acylation sequence may be employed for the synthesis of macrolides including (±)-recifeiolide and (±)-di-0-methylcurvularin.

The conversion of α-bromo-β-dicarbonyls to vicinal tricarbonyls using dimethyldioxirane and base

Abstract Vicinal tricarbonyls are prepared from α-bromo-β-dicarbonyl precursors by base promoted oxygen transfer from dimethyldioxirane. The α-bromo-β-dicarbonyls were prepared by the reaction of CuBr2 and [hydroxy(tosyloxy)iodo]benzene (Koser’s reagent) with a β-dicarbonyl system.

Vicinal Tricarbonyl products from singlet oxygen reactions.: Application to the synthesis of carbacephams.

Abstract Vicinal tricarbonyl systems are readily formed by reacting β-dicarbonyl precursors with DMF acetal to form enamines which are then cleaved by photooxidation. This procedure may be applied to the formation of carbacephams.

β-Lactams as building blocks in the synthesis of macrocyclic spermine and spermidine alkaloids

Abstract Syntheses of the macrocyclic spermidine alkaloids (±)-celacinnine ( 1 ) and (±)-dihydroperiphylline ( 2 ) as well as the related spermine alkaloid (±)-verbascenine ( 3 ) were accomplished by means of sequential ring expansions of smaller lactam rings. Three ring expansion methods were employed: (1) transamidation of N -(aminoalkyl)lactams, (2) β-lactam-lactim ether condensation followed by reductive cleavage of the bicyclic 4-oxotetrahydropyrimidine product with NaBH 3 CN/AcOH and (3) bicyclic acyl hydrazine formation followed by N–N bond cleavage with Na/NH 3 . Each synthesis features ring expansion of a 4-phenylazetidin-2-one intermediate that undergoes transamidative ring expansion or lactim ether condensation.

The use of β-lactams in the synthesis of spermine and spermidine alkaloids : Total synthesis of homaline

Abstract The optically active plant product homaline ( 6 ) has been synthesized in a convergent sequence starting with β-phenyl-β-alanine and putrescine ( 14 ) The key transformation in this sequence is the ring expansion by transamidation of a functionalized chiral β-lactam precursor

Alkenyl tricarbonyl derivatives of α-amino acids as trielectrophiles. Formation of heterocyclic-substituted products

Abstract Alkenyl tricarbonyl esters have been prepared by reaction of mono aldehydes of dibasic amino acids with tricarbonyl esters. These systems undergo reaction with diamines and other dinucleophiles by a combination of Michael addition and nucleophilic attack at the electrophilic central carbonyl to form pyrrole derivatives. These monoaldehydes may also be used to incorporate imidazole and furan residues into the amino acid starting materials.

The conversion of car☐ylic acids to keto phosphorane precursors of 1,2,3-vicinal tricarbonyl compounds

Abstract Acyl phosphoranylidines react with acid chlorides or anhydrides in the presence of bis(trimethylsilyl)acetamide (BSA), or couple directly with car☐ylic acids activated by EDCI to give keto phosphoranes 1 .