Synthesis of esters of 4-hydroxy-5-phosphinyl-2-imidazolidinone

The esters of 4-hydroxy-5-phosphinyl-2-imidazolidinone were prepared by reaction of urea with the esters of 2-hydroxy-2-phosphinylethanal in acidic medium. The ir, ¹H nmr and ³¹P nmr spectral data of the products are reported. All the isolated products had cis configuration. The stereochemistry of their formation is discussed.     

Studies toward diazonamide A: initial synthetic forays directed toward the originally proposed structure

A brief introduction into the chemistry of diazonamide A (1) is followed by first-generation sequences to access the originally proposed structure for this unusual marine natural product. These explorations identified a route capable of delivering a model compound possessing the complete heteroaromatic core of the natural product, highlighting in the process several unanticipated synthetic challenges which led both to new methodology as well as an improved synthetic plan that was successfully applied to fully functionalized intermediates.     

Studies toward diazonamide A: development of a hetero-pinacol macrocyclization cascade for the construction of the bis-macrocyclic framework of the originally proposed structure

In this article, we describe further studies toward the originally proposed structure of diazonamide A (1). After confronting a number of failures in synthesizing the heterocyclic core of that structure, success was finally realized through the development of a novel hetero-pinacol-based macrocyclization cascade sequence. Subsequent elaboration led to an advanced compound bearing both of the 12-membered rings of the target molecule. In addition, preliminary biological studies with intermediates and simplified analogues obtained via the developed sequences are also described.     

Conformational analysis of amphetamine in solution based on unambiguous assignment of the diastereotopic benzylic protons in the 1H NMR spectra

The erythro- and threo-amphetamine-β-d diastereomers were synthesized and used for the unambiguous assignment of the diastereotopic benzylic protons and the measurement of vicinal ¹H-¹H coupling constants which were used to determine the distribution of rotamers around the central c_α-c_β bond in the side chain.     

Polymer brushes on periodically nanopatterned surfaces

Structural properties of polymer brushes tethered on a periodically nanopatterned substrate are investigated by computer simulations. The substrate consists of an alternating succession of two different types of equal-width parallel stripes, and the polymers are end-tethered selectively on every second stripe. Three distinct morphologies of the nanopatterned brush have been identified, and their range of stability has been determined in terms of a single universal parameter that combines the grafting density, the polymer length, and the stripe width. We propose scaling relations for the average brush height and for the architectural properties of the outer surface of the nanopatterned brush under good solvent conditions. Our analysis provides guidelines for fabricating well-defined and tunable nanopatterned polymeric films.     

Interaction of functional dendrimers with multilamellar liposomes: design of a model system for studying drug delivery

Multilamellar liposomes consisting of phosphatidylcholine-cholesterol-dihexadecyl phosphate (19:9.5:1 molar ratio) and dispersed in aqueous or phosphate buffer solutions were interacted with poly(propylene imine) dendrimers which were partially functionalized with guanidinium groups. The remaining toxic external primary amino groups of the dendrimers were reacted with propylene oxide, affording the corresponding hydroxylated derivatives. Microscopic, zeta-potential, and dynamic light scattering techniques have shown that liposomal-dendrimeric molecular recognition occurs due to the interaction between the complementary phosphate and guanidinium groups. Calcein liposomal entrapment experiments demonstrate a limited leakage, i.e., less than 13%, following liposomes interaction with the modified dendrimers. Calorimetric studies indicate that the enthalpy of the interaction is dependent on the number of guanidinium groups present at the dendrimeric surface and the medium. The process is reversible, and redispersion of the aggregates occurs by adding concentrated phosphate buffer. Two corticosteroid drugs, i.e., betamethasone dipropionate and betamethasone valerate, were encapsulated into the functionalized dendrimers. Drug transport from guanidinylated dendrimers to multilamellar liposomes ranges from 40% to 85%, and it is also dependent on the medium and the degree of dendrimer guanidinylation.     

Click production during breathing in a sperm whale (Physeter macrocephalus)

A sperm whale (Physeter macrocephalus) was observed at the surface with above- and underwater video and synchronized underwater sound recordings. During seven instances the whale ventilated its lungs while clicking. From this observation it is inferred that click production is achieved by pressurizing air in the right nasal passage, pneumatically disconnected from the lungs and the left nasal passage, and that air flows anterior through the phonic lips into the distal air sac. The capability of breathing and clicking at the same time is unique among studied odontocetes and relates to the extreme asymmetry of the sperm whale sound-producing forehead.     

Formation of new alkynyl(phenyl)iodonium salts and their use in the synthesis of phenylsulfonyl indenes and acetylenes

The preparation of phenylsulfonyl indene derivatives and phenylsulfonyl- acetylenes from readily available alkynyl(phenyl)iodonium tetrafluoroborates and triflates was investigated using phenylsulfinate as nucleophile.     

Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases

A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR(1) and the tylKR(1) domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and stereospecificity, even though the substrate is not tethered to an acyl carrier protein or an intact PKS multienzyme. In contrast, and to varying degrees, the isolated enzymes eryKR(2), eryKR(5), and eryKR(6) exercised poorer control over substrate selection and the stereochemical course of ketoreduction. These data, together with modeling of diketide binding to KR(1) and KR(2), demonstrate the fine energetic balance between alternative modes of presentation of ketoacylthioester substrates to KR active sites.