Introduction of axial chirality at a spiro carbon atom in the synthesis of pentaerythritol-imine macrocycles.

Novel chiral macrocyclic polyimines with spiro carbon atoms are described. The key feature of the synthesis is the formation of an axially chiral quaternary carbon atom having four constitutionally identical substituents. This is possible either by the freezing of the labile conformation of a spiro-diboronate moiety or by the diastereomeric fitting of a conformationally stable spiro-acetal moiety into a chiral framework. A general model for the description of this type of axial chirality is proposed.

The significance of induced circular dichroism.

[reaction: see text] Achiral molecules or ions can display induced circular dichroism (ICD) within their absorption bands on association with chiral inducing molecules. The reverse process is equally important, although less appreciated: chiral inducing molecules, such as tartrates, can show significantly differing CD bands in different achiral environments. Therefore true ICD due to achiral molecules can only be demonstrated in the spectral region outside the absorption bands of the chiral inducing molecules. The case of tartrate-trisimidazoline helical assembly in aqueous solvent is discussed.

Architecture and function of atropisomeric molecular triads.

Molecular triads, B-A-B, in which the central unit A is aromatic or heteroaromatic, can exist as syn or anti conformers or atropisomers of correspondingly C or S shape. These stereoisomers are either discrete conformer species, often distinguished by NMR spectroscopy, or can be separated at ambient temperature as stable atropisomers. In the latter case syn and anti stereoisomers exhibit different (e.g., complex-forming) properties. Practical applications of atropisomeric triads as ligands in asymmetric dihydroxylation are also discussed.

Lactones. 6. Microbial lactonization of gamma,delta-epoxy esters.

The ability of 19 microorganisms to perform the enantioselective lactonization of racemic gamma,delta-epoxy ester 3a and its 7-methyl homolog 3b was checked. It was found that Rhodotorula rubra preferentialy transformed both substrates to (-)-enantiomers of trans delta-hydroxy-gamma-lactones with ee 76% for 3a and 24% for 3b. The best efficiency (20-30%) and enantioselectivity (ee 60-100%) of formation of (-)-gamma-hydroxy-delta-lactones 6a and 6b was observed for lactonization by Botrytis cinerea and Fusarium semitectum, respectively.

Chiral C and S conformers of aromatic diimide triads.

Chiral triads composed of a central aromatic diimide moiety and two outer aromatic molecules connected by one- or two-carbon linkers exist in an equilibrium of C and S conformers, as inferred from analysis of circular dichroism and nuclear magnetic resonance spectra, as well as from molecular modeling.

Designing large triangular chiral macrocycles: efficient

Triangular 30- and 27-membered hexaiminomacrocycles 4 and 5 of D(3) and C(3) symmetry, respectively, are readily obtained by unprecedented [3 + 3] cyclocondensation of (R,R)-1, 2-diaminocyclohexane with, accordingly, terephthalaldehyde and isophthalaldehyde. The course of the reaction, leading to macrocyclization, is governed by conformational constraints imposed on the structural components of the intermediate products, as shown by molecular modeling. X-ray analysis of cocrystal 4.AcOEt revealed that the macrocycle symmetry significantly departs from ideal D(3) symmetry due to crystal environment. Cyclic hexaamines 6 and 7 were prepared by sodium borohydride reduction of 4 and 5, respectively.

Chirality of aromatic bis-imides from their circular dichroism spectra

It is demonstrated that chirality of molecules composed of 1,2,4, 5-benzenetetracarboxydiimide (pyromellitic diimide) or 1,4,5, 8-naphthalenetetracarboxydiimide units is reflected by their exciton Cotton effects. The analysis is based on the calculated (ZINDO/S) excited states of the model diimide chromophores 1a and 2a. Rotation of the diimide chromophores around the C-N bond in diimides 3-5 is evaluated from the dynamic (1)H NMR data. A comparison of chiroptical properties of bis-diimides 3-5 with the CD spectra of bis-imides 6-8 is also presented. Copyright 2000 Wiley-Liss, Inc.

1,8-Naphthalimides as Stereochemical Probes for Chiral Amines: A Study of Electronic Transitions and Exciton Coupling.

The absorption and magnetic circular dichroism (MCD) spectra of 1,8-naphthalimide are analyzed in terms of the number of contributing electronic transitions and their polarization. The experimental results are supported by semiempirical INDO/S calculations. It is demonstrated that the strongly allowed, pi --> pi naphthalene transition of the 1,8-naphthalimide chromophore located at 231 nm is perfectly suited for absolute configuration assignments of amine derivatives on the basis of the bichromophoric exciton coupling. Both degenerate (bis-1,8-naphthalimide) and nondegenerate (1,8-naphthalimide-phthalimide, 1,8-naphthalimide-phenyl, or 1,8-naphthalimide-benzoate) couplings were studied. In the latter case, the sign of the exciton Cotton effect was opposite to the sign of the degenerate exciton Cotton effect for the same absolute configuration. An extension of the application of the exciton coupling to the 264 nm pi --> pi transition of 1,9-anthraimide is also shown.

Long-acting contraceptive agents: testosterone esters of unsaturated acids.

The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens.

PIP: A program of the World Health Organization for developing long-acting esters of testosterone that would exhibit a more constant release rate and maintain testosterone levels in the normal range longer than testosterone enanthate found that these esters had a role in fertility, and gerontology. The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic or polyunsaturated functions in the chain, for evaluation as long-acting androgens. The nuclear magnetic resonance (NMR) images were recorded on a spectrometer. The samples were recorded in tubes using CDC13 as solvent. The NMR spectra were recorded with Perkin-Elmer instrument in CDC13, with tetramethylsilane as internal reference. Infrared spectra were measured on the same spectrometer. Mass spectra were also recorded. Thin-layer chromatography was performed on Merck silica gel and the spray reagent was iodine or vanillin. To a solution of testosterone the corresponding acid chloride was added yielding the pure ester after the usual work-up. E-5-methylhexa-2,4-dienoic (IXb), 5- phenylpenta-2-,4-dienoic (Xb), 5-phenyl-4-yn-pent-2-enoic (XIb), and non-4-en-6-ynoic acid (XIIb), were required for the synthesis. Esterification of testosterone with each of the first 12 unsaturated acids was performed by reaction with the corresponding acid chlorides in pyridine. Although the nona-2,3-dienoic acid ethyl ester was easily obtained, this compound could not be hydrolyzed to the acid (XIIIb). Hence, an alternative procedure was tried for the synthesis of the ester XIIIa, by reaction of bromoacetate of testosterone (XIVa) with triphenylphosphine to give the phosphorane (XVa). Reaction of this phosphorane (XVa) with 1-diazoheptan-2-one (XVI) led to the allenic ester (XIIIa).

Long-acting contraceptive agents: furylalkylcarboxylic acid esters of norethisterone.

5-Methyl- and 5-ethyl-furylalkylcarboxylic esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) were prepared in high yield in the presence of thallous ethoxide. The activities of these compounds as long-acting contraceptive agents have been evaluated.