No abstract

The structural properties of the phosphoglycerol polar head group in bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol have been studied with deuterium and phosphorus-31 nuclear magnetic resonance. For this purpose, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol was deuterated chemically or biosynthetically at all three segments of the glycerol head group. Both the D and the L configurations of the glycerol head group have been synthesized, and the correct stereochemical configuration of the polar group was verified by an enzymtic assay, as direct measurement of the optical rotation was insufficiently sensitive to distinguish between these diastereomers. The phosphatidylglycerol sodium salts were dispersed in excess buffer (0.1 M NaCl, pH 7.0), and the bilayer properties were characterized by small-angle X-ray diffraction and differential scanning calorimetry. The deuterium quadrupole splittings, delta vQ, and the phosphorus-31 chemical shielding anisotropy, delta sigma, were measured as a function of temperature in the range 20-60 degrees C, yielding the following results. (1) Well-resolved deuterium signals were obtained for all head-group segments and could be assigned unambiguously. (2) Almost identical spectra were obtained for 1,2-dipalmitoyl-sn-glycero-3-phospho-1'-glycerol (natural L,D configuration) and 1,2-dipalmitoyl-sn-glycero-3-phospho-3'-glycerol (L,L configuration), suggesting very similar head-group motions and orientations for both diastereomers. (3) The spatial anisotropy of motion and the segmental fluctuations of the negatively charged phosphoglycerol are similar to those of the zwitterionic phosphocholine and phosphoethanolamine head groups but differ distinctly from those of phosphoserine which also carries a net negative charge. (4) The motional inequivalence of geminal deuterons in 1,2-dipalmitoyl-sn-glycero-3-phospho-3'-glycerol was demonstrated by synthesis of a stereospecifically monolabeled analogue.

SummaryPig liver esterase-(PLE) catalyzed hydrolysis of dimethyl esters of symmetrical dicarboxylic acids, including meso-diacids, cis-1,2-cycloalkanedicarboxylic acids, and diacids with a prochiral center, was studied with 14 substrates. The products of these stereoselective hydrolyses are chiral monoesters of dicarboxylic acids, with an enantiomeric excess (e.e.) from 10% to 100%. Some of these optically active monoesters are valuable synthons in natural products synthesis.An additivity pattern of a-and /3-substituents with the glutaric esters on the stereoselectivity of enzymatic hydrolysis was observed. Analysis of the experimental results leads to a model of enzyme stereoselectivity of diester hydrolysis in which the substitution pattern at a-and a-C-atoms is found to determine the absolute configuration of the resulting monoester.The control of absolute stereochemistry is of fundamental importance for natural product synthesis [l]. Although a plethora of chemical methods has been developed for the construction of optically active compounds [2], the unique opportunity provided by enzymes as catalysts in asymmetric synthesis is being increasingly exploited [3].It is theoretically possible, by utilizing the enantioselectivity of enzymes towards meso-compounds and compounds with a prochiral center to transform the total amount of starting material into a target molecule. The classical example of this kind of transformation represents the synthesis of (R)-mevalonolactone using the high selectivity provided by pig liver esterase (PLE) towards dimethyl 3-hydroxy-3-methylglutarate [4]. From a preparative standpoint it is important to note that by appropriate manipulation of the functional groups (S)-mevalonolactone can also be synthesized.We can envisage that by using enzymes which possess low substrate selectivity but which at the same time catalyze reactions with a high degree of stereoselectivity, a large number of new chiral synthons can be provided. a-Chymotrypsin [5], horse liver alcohol dehydrogenase [6], PLE [7], and some other esterases from different microorganisms [8] have already been used to provide chiral synthons of highest optical purity for the synthesis of natural products.

No abstract

SummaryA general scheme for the synthesis of the tetrahydroisoindolinone moiety of naturally occurring cytochalasans and unnatural analogs was developed. The keystep consists of the intermolecular [2 + 4lcycloaddition of 4-methylsorbinol (7) to an alkylidene malonic ester derivative such as 6, 9 or 10, obtained from the corresponding amino acids. The products obtained, 4a, 17, and 18 were converted to the desired lactams 5,21, and 22.Cycloaddition of the diene alcohol 7 to the optically active alkylidene malonic ester derivative 9b (s. Footnote 5) prepared from L-leucine gave compound 17b with 98% enantiomeric excess. The optical activity was retained during the conversion of 17b to the lactam 21b. The latter is a subunit for the synthesis of the aspochalasins.In a recent paper describing a convenient synthetic approach to the tetrahydroisoindolinone nucleus of proxiphomin (1) (cJ: Scheme I) [l] we discussed the stereochemical course of an intramolecular [2 + 4lcycloaddition of the alkylidene 4-methylsorbyl esters 2a and 2b to the expected anellated cyclohexene intermediates 3 a and 3b. These should yield the tricyclic species 4 a and 4b, respectively, by subsequent lactam ring closure. Evidence was presented that the (2)-olefin 2a leads to a product of structure 4a with correct relative configurations at C(3), C(4), C(5), and C(8), but with 'unnatural' configuration at C(9)4). Also an efficient procedure for the epimerization at C (9) leading to the tetrahydroisoindolinone 5 was described. However, the key intermediate 4a was obtained only in low yield.