Biomedical subjects
Publications and source records attributed to S D Burke.
The results of a single-crystal X-ray experiment and density functional theory calculations performed for the title compound, C20H22O4, demonstrate that the lowest energy conformation of this molecule does not contain C2 molecular symmetry.
[see reaction]. A novel palladium-mediated, ligand-controlled double cyclization is reported. The C2-symmetric diene produced was desymmetrized via Sharpless asymmetric dihydroxylation and was further transformed into a known intermediate in the synthesis of uvaricin.
[figure: see text] Formal synthesis of the naturally occurring deaminated sialic acid KDN, a potential oncofetal antigen, has been accomplished in 45% overall yield via a novel ketalization/ring-closing metathesis sequence. The rapid introduction of all oxygen functionality in a completely stereocontrolled manner exploited a rigid 6,8-dioxabicyclo[3.2.1]oct-2-ene ring system. This general synthetic strategy should provide access to a number of KDN and sialic acid analogues.
A short and efficient synthesis of the C(1)-C(15) subunit of halichondrin B in its natural configuration is described. The polycyclic caged ketal 3, containing nine asymmetric centers, is prepared in 14 steps from alpha-D-glucoheptonic acid gamma-lactone (7). Key steps in the two similar routes described include EtMgBr-promoted pinacol ring expansions of hydroxy mesylates 23 and 34, intramolecular Michael additions of 29 and 37, and a one-pot, HF-induced conversion of 4 to 3involving in situ silyl ether cleavage, acetal hydrolysis, Michael addition, and caged ketal formation. Alternative protocols for carbinol inversion at C(11), one early and one late in the synthetic sequence, are also described.
Amides and esters have been synthesized from 2,2,2-trihaloethyl esters in one pot using phosphorus-(III) reagents as reductants, with resultant carboxylate activation as an acyloxyphosphonium intermediate, and in situ trapping by amine or alcohol nucleophiles. Secondary and tertiary amides were synthesized, including a dipeptide, in good yields using hexamethylphosphorous triamide (Me2N)3P, as reducing agent. Optimal yields of esters derived from primary and secondary alcohols were obtained using tributylphosphine and DMAP. Tribromoethyl esters provided yields superior to those obtained with trichloroethyl esters.
Modular syntheses of C(3)-symmetric macrocycles with pendant aryl and hydroxymethyl groups are described. These functional groups, amenable to further elaboration, were installed early in each synthesis and carried through an iterative sequence of module coupling and macrolactonization. Association constants for macrolides 1a-c with alkali metal cation guests were determined, and sandwich-type complexes with Ba(2+) were confirmed for these macrocycles based on (1)H NMR studies, including Job plots. X-ray crystallographic data for macrolides 1a and 1c were obtained and are discussed in detail. These data provide support that the macrolides are structurally well-defined and preorganized for binding the potassium cation. Preparation of the tris(bromoacetylated) macrotriolide 43 exemplifies a functionalized platform suitable for elaboration with peptide or carbohydrate residues.
[formula: see text] The 6,8-dioxabicyclo[3.2.1]octane skeleton is a common structural subunit in natural products. A conceptionally new strategy affording these structures is described for the syntheses of (+)-exo-brevicomin and rac-endo- and enantiomerically enriched (+)-endo-brevicomin, employing desymmetrization of trienes derived from diols with C2 and meso symmetry via ring-closing metathesis.
[formula: see text] Total syntheses of KDO and 2-deoxy-beta-KDO are reported. The C2-symmetric dienediol 4 was desymmetrized by conversion to its corresponding 1,4-dioxanone 5. Ireland-Claisen rearrangement of 5 provided the 6-vinyldihydropyran-2-carboxylate template 6. Double-Sharpless asymmetric dihydroxylation gave the tetraol 7a, which was converted to KDO and 2-deoxy-beta-KDO using methods similar to those previously reported. This synthetic scheme provides a flexible route to KDO and KDO analogues.
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PURPOSE: The objective of this study was to assess the impact of young maternal age and the timing of conception on birth weight among primiparous women living in Gibraltar. METHODS: The data for this study were derived from a population of 295 primiparous women who gave birth under 25 years of age. Only married women who had no previous maternal history and delivered live singleton newborns between 1980 and 1984 were included. The confounding effects of gestation length, sex, and socio-economic status on birth weight were taken into account using the multivariate technique of multiple classification analysis. A conception timing variable was constructed and partitioned into four groups which represented the separate and joint effects of maternal age and prenuptial stress on birth weight. RESULTS: The overall mean birth weight was 3344.15 g. After controlling for the specified factors and covariate, the infants of older mother (> 19) who conceived after marriage weighed 57.78 g above the referent group mean. Older mothers who conceived a child before marriage delivered infants weighing 75.67 below the grand mean. Young mother (< 20) who conceived within marriage had infants who weighed 37.32 g less than the grand mean. Infants delivered by young mothers who conceived before marriage weighed 133.66 g less than the overall mean birth weight. The only significant group difference detected within the conception timing variable was between young mothers who conceived before marriage versus older mothers who conceived after marriage. CONCLUSIONS: Premarital conception is identified as a risk factor for lower infant birth weights among mothers under 20 years of age. This study emphasizes the need to take into account the effects of culturally mediated behavior on the pregnancy experience of young women.
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