4669-02-7

The glycinocins are a class of calcium-dependent, acidic cyclolipopeptide antibiotics that are structurally related to the clinically approved antibiotic daptomycin. In this article, we describe the synthesis of a small library of glycinocin analogues that differ by variation in the exocyclic fatty acyl substituent. The glycinocin analogues were screened against a panel of Gram-positive bacteria (as well as Gram-negative P. aeruginosa). These analogues exhibited similar calcium-dependent activity to the parent natural products against Gram-positive bacteria but showed no activity against P. aeruginosa. The length of the fatty acid was shown to be important for optimal biological activity, while the hybridisation at the α,β position and branching within the fatty acyl chain had only subtle effects on activity.

We report a concise asymmetric synthesis of rakicidin A, a macrocyclic depsipeptide that selectively inhibits the growth of hypoxic cancer cells and stem-like leukemia cells. Key transformations include a diastereoselective organocatalytic cross-aldol reaction to build the polyketide portion of the molecule, a highly hindered ester fragment coupling reaction, an efficient Helquist-type Horner - Wadsworth - Emmons (HWE) macrocyclization, and a new DSC-mediated elimination reaction to construct the sensitive APD portion of rakicidin A. We further report the preparation of a simplified structural analogue (WY1) with dramatically enhanced hypoxia-selective activity. Take my breath away: Rakicidin A, a depsipeptide natural product with hypoxia-selective antitumour activity, is comprised of a ring system containing sensitive and congested functionalities. A modular asymmetric synthesis and initial biological evaluation of the natural product, and the discovery of a simplified analogue displaying strongly enhanced hypoxia selectivity is reported.

A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C 12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C 15-C17) and hexadecanolide (for iso-C18-C 19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

To provide a method for performing a cross-coupling reaction of a Grignard compound with an alkyl halide simply, efficiently and in high yield, a method for obtaining a ω-bromo long chain carboxylic acid simply and efficiently using an easily obtainable raw material and a method for producing a useful branched fatty acid simply and efficiently. [R1: an alkyl group having 1 to 15 carbon atoms, R2: an alkyl group having 1 to 30 carbon atoms with a carboxyl group and X and X': a halogen atom] [n : an integer of 9 to 17] [n : an integer of 9 to 17, R1a : a branched alkyl group having 3 to 8 carbon atoms and X: a halogen atom]

Host marking pheromones (HMPs) are used by insects to mark hosts (usually a fruit) where they have already laid eggs. The compounds serve as a deterrent to conspecifics avoiding over-infestation of hosts (i.e. repeated egg-laying into an already occupied/used host). If these HMPs are sprayed onto commercially valuable fruit they act as deterrents preventing attack by females interested in laying eggs into the valuable commodity. Having no insecticidal or toxic properties, and being natural products (or close derivatives thereof) they could be used as fruit sprays to replace insecticides, or in combination with other products to improve efficacy. This review discusses the isolation, and synthesis of the HMP of the Mexican fruit fly Anastrepha ludens a feared pest of citrus and mangos in Mexico and Central America. This compound is also recognized by females of other pestiferous species in the same genus Anastrepha distributed from the Southern USA to Northern Argentina, including many Caribbean Islands. The synthetic HMP was shown to exhibit strong electrophysiological activity against A. ludens and excellent interspecies cross recognition with other Anastrepha species. Behavioural tests confirmed the HMP deterring effect of the synthetic natural product. Further studies enabled us to drastically simplify the structure of the HMP and obtain a derivative, which we named Anastrephamide, which shows HMP deterring effects very similar to the natural product in laboratory and field tests. The potential use of such HMP derivatives in a crop protection scenario is briefly discussed. Schweizerische Chemische Gesellschaft.

Septacidin analogs, useful as antitumor agents, having the structure STR1 where R is a branched or straight chain alkanoyl group of from 12 to 16 carbon atoms. A preferred compound is 6-[4,6-dideoxy-4-(isopalmitoylglycyl)-amino-β-L-glucopyranosylamino]-9H