Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.

Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. AC1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid.

Marine macrolides: an improved second-generation total synthesis of the anticancer macrolide spirastrellolide A methyl ester has been achieved. The synthesis features a uniformly high level of stereocontrol combined with more expedient fragment assembly, and demonstrates a critical dependence of the crucial macrolactonization step on the substitution pattern of the C22-C24 linker region.

Introduction As the incidence and death rate of injury are relatively high in Korea, the public health concerns are now increasing. The aim of this study are (1) to describe the regional distribution and pattern of the injury prevalence, (2) to evaluate the relationship between the Korea poverty index and the regional variation of the injury. Methods <2009 Korea Community Health Survey> was the national interview survey in Korea. The type of injury was categorised by ICECI and the age adjusted injury prevalence was calculated. The regional variation was evaluated by the index; EQ (Extremal Quotient), CV (Coefficient of Variation), CVA (CV from ANOVA). For explaining the effect of Korea poverty index to regional variation, general linear model was applied. Results The 1-year experience of all kinds of injury was more prevalent to men than to women. Falls (30%) was most frequent type of injury. The significant regional variation was found according to the category of injury. In the urban area, the 1-year experience rate of all kinds of injury was 5.47 (4.39–6.54) in poorest region by Korea poverty index, and 4.61 (4.28–4.94) in richest region. The statistically significant linear trend was found across the quartile of poverty index (p for trend =0.04). Discussion There were significant regional variations according the rurality, administrative regions, and the Korea poverty index. For the tackling the high prevalence and regional discrepancy of the injury, community specialised and area based intervention were needed.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The optimisation of a synthetic strategy towards the ABC segment of the cytotoxic macrolide spirastrellolide A is reported, together with its application to the synthesis of two diastereomeric C-1 - C-22 fragments for stereochemical correlation purposes with a putative spirastrellolide degradation product.

Abstract Progress toward a total synthesis of spirastrellolide A, a 38-membered marine macrolide, is reported. Syntheses of two diastereomers of the C1-C25 region, and an evolving Sharpless dihydroxylation strategy toward a C26-C40 fragment, are described. The syntheses exploit boron-mediated aldol chemistry to install key stereocenters, and feature late-stage thermodynamically controlled spiroacetalizations.

An efficient synthesis of the C-26-C-40 tricyclic [5,6,6]-bis-spiroacetal segment of the marine macrolide spirastrellolide A has been developed, exploiting a novel double Sharpless asymmetric dihydroxylation/spiroacetalisation sequence.