1H NMR study of protected and unprotected kainoid amino acids: facile assignment of C-4 stereochemistry

The kainoid amino acids exhibit potent neuroexcitatory activity in the mammalian central nervous system. Around their pyrrolidine ring, a trans disposition between the C-2 and C-3 substituents and a cis relationship between the C-3 and C-4 substituents are crucial for their potent biological activity. During synthetic studies into the kainoids, we have established a straightforward, empirical rule, which allows the facile assignment of C-4 stereochemistry to both protected and unprotected kainoids. When pairs of C-4 epimers are available, the rule indicates that, when their (1)H NMR spectra are compared, one of the methylene protons on the C-3 side chain appears at significantly lower chemical shift in the C-3, C-4 cis isomer than the corresponding signal for the proton in the spectrum for the C-3, C-4 trans isomer. In addition, the rule states that the difference in chemical shift between the two individual protons on the C-3 side chain of the C-3, C-4 cis isomer is significantly greater than the corresponding difference for the C-3, C-4 trans isomer. The rule is demonstrated for kainoids possessing an unsaturated substituent at C-4 and when comparing spectra in D(2)O for pairs of unprotected C-4 epimers, the spectra were recorded at approximately the same pD.     

Characteristics of the mass spectra of ecdysteroids with different numbers of -OR groups

The mass spectra of 15 phytoecdysteroids and acetyl derivatives have been compared. With a decrease in the number of -OR groups, the contribution of cleavages of the bonds of the steroid skeleton increases. 20,22-Diols are characterized by the greatest significance of fragmentation at the C-20–C-22 bond. In all the spectra, clear indications of fragmentation of the side chain at the C-22–C-23, C-23–C-24, and C-24–C-25 bonds are observed.     

Biosynthetic study of amphidinolide W

The biosynthetic origins of amphidinolide W (1) were investigated on the basis of (13)C-NMR data of 13C-enriched samples obtained by feeding experiments with [1-13C], [2-13C], and [1,2-13C2] sodium acetate in cultures of a strain Y-42 of the dinoflagellate Amphidinium sp. These incorporation patterns suggested that 1 was generated from a hexaketide chain, two acetate units, four isolated C1 units from C-2 of acetates, and four branched C1 units from C-2 of acetates. The acetate-incorporation patterns for C-1-C-2-(C-21) and C-8-C-18-(C-23, C-24) of 1 corresponded well to those for C-1-C-2-(C-27) and C-5-C-15-(C-28, C-29) of amphidinolide H (2) isolated from this strain.     

New cytotoxic bufadienolides from the biotransformation of resibufogenin by Mucor polymorphosporus

Resibufogenin is a cytotoxic steroid isolated from the Chinese drug ChanSu. The biotransformation of resibufogenin by Mucor polymorphosporus afforded 22 products, and 15 of them were new. The transformation reactions involved hydroxylations at C-1β, C-5, C-7α, C-7β, C-12α, C-12β and C-16α, as well as epimerization or dehydrogenation of 3-OH. Hydroxylations at C-12α, C-12β and C-16α were the major reactions, each giving products in >5% yields, whereas the other products were obtained in fairly low yields. Some of the products showed decreased but still potent cytotoxicities. This investigation provided a useful approach to prepare new bufadienolides and most of them were difficult to obtain by chemical means.     

Amphidinolide T, novel 19-membered macrolide from marine dinoflagellate Amphidinium sp

A novel 19-membered macrolide, amphidinolide T (1), has been isolated from a marine dinoflagellate Amphidinium sp., and the structure was elucidated on the basis of spectroscopic data. Relative stereochemistry at C-7, C-8, and C-10 was deduced from the NOESY correlations, while absolute configurations at C-2, C-13, C-14, and C-18 were assigned on the basis of NMR data of the MTPA esters of 1 and those of degradation products of 1.     

Solid-state photodimerization of cholest-4-en-3-one

Crystalline cholest-4-en-3-one undergoes solid-state dimerization by UV radiation to give two ring A - ring A connected dimers. No dimerization occurs in solution. The first dimer, characterized by a cyclobutane ring, is formed by connection of C-2 and C-3 of a moiety with C-5' and C-6' of another moiety, respectively. The latter dimer has a six-membered ketal ring formed by connection of C-2 with C-5' and of O, linked to C-3, with C-3'. The structures have been determined by spectroscopic means. X-ray analysis of title compound evidences the proximity of the axial H-2 of a molecule to the C-4' of a molecule in the upper layer. The transfer of the hydrogen and the connection between C-2 and C-5' might be the driving force of dimerization.     

Mass spectroscopy of natural products. VI—Localization of functional groups in the hopane skeleton

The mass spectral fragmentation of hopane derivatives with oxygenated substituents at C-3, C-6, C-7, C-15, C-16 and C-22 is discussed. It is shown, that the positions of functional groups in rings A and B or D and E respectively can be distinguished using several derivatives and deuterated analogues.     

Cal-B-catalyzed alkoxycarbonylation of a-ring stereoisomeric synthons of 1alpha,25-dihydroxyvitamin D3 and 1alpha,25-dihydroxy-19-nor-previtamin D3: a comparative study. first regioselective chemoenzymatic synthesis of 19-nor-A-ring carbonates

A comparative study of alkoxycarbonylation processes of both 19-nor-A-ring and A-ring stereoisomers of 1alpha,25-dihydroxyvitamin D3 analogues catalyzed by Candida antarctica lipase B (CAL-B) has been described. The presence of the methyl group in the A-ring at C-2, as in 3-6, has a determining role in the regioselectivity of the biocatalysis, mainly allowing the hydroxyl group at C-5 position to react. For the 19-nor-A-ring stereoisomers 7-10, which lack the C-2 methyl group, the configurations at C-3 and C-5 have a high influence in the selectivity exhibited by CAL-B. Thus, each couple of enantiomers showed opposing regioselectivities depending on the C-3 configuration. When C-3 possesses an (S)-configuration, enzymatic alkoxycarbonylations took place at the C-5-(R) or C-5-(S) hydroxyl groups. However, if the chiral centers at C-3 are (R), CAL-B alkoxycarbonylated the C-3-(R) hydroxyl group independently of the configuration at C-5. The corresponding carbonates are useful A-ring precursors of 1alpha,25-dihydroxyvitamin D3 analogues, selectively modified at the C-1 or C-3 positions. In addition, an improved synthesis of cis A-ring synthons 5 and 6 is described using a Mitsunobu methodology.     

Carbon-13 nuclear magnetic resonance spectra. VIII—18α- and 18β-glycyrrhetic acid derivatives

The ¹³C NMR data of six pairs of 18α/18β-glycyrrhetic acid derivatives are presented. It is shown that the configuration at C-18 can easily be recognized by inspecting the chemical shifts of several characteristic carbons, e.g. C-12, C-13, C-18 and C-28. The shifts of these carbons originated by the change of the D/E ring junction proved to be largely independent of the substitution at C-3 and C-20.     

Amphidinolides T2, T3, and T4, new 19-membered macrolides from the dinoflagellate Amphidinium sp. and the biosynthesis of amphidinolide T1.

Three new 19-membered macrolides, amphidinolides T2 (2), T3 (3), and T4 (4), structurally related to amphidinolide T1 (1) have been isolated from two strains of marine dinoflagellates of the genus Amphidinium. The structures of 2-4 were elucidated on the basis of spectroscopic data. The absolute configurations at C-7, C-8, and C-10 of 1-4 were determined by comparison of NMR data of their C-1-C-12 segments with those of synthetic model compounds for the tetrahydrofuran portion. The biosynthetic origins of amphidinolide T1 (1) were investigated on the basis of 13C NMR data of a 13C enriched sample obtained by feeding experiments with [1-(13)C], [2-(13)C], and [1,2-(13)C2] sodium acetates and 13C-labeled sodium bicarbonate in the cultures of the dinoflagellate. These incorporation patterns suggested that amphidinolide T1 (1) was generated from four successive polyketide chains, an isolated C1 unit formed from C-2 of acetates, and three unusual C2 units derived only from C-2 of acetates. Furthermore, it is noted that five oxygenated carbons of C-1, C-7, C-12, C-13, and C-18 were not derived from the C-1 carbonyl, but from the C-2 methyl of acetates.     

Remote functionalization on the steroid β-face: Attack on an angular methyl group,and into the sidechain

Benzophenonealkanoate esters of 6-β-cholestanes insert photolytically into C-15, C-16, and the C-18 methyl, or into C-23 and C-25 of the sidechain, depending on the length of the attaching chain.     

Mobile Phase Selectivity in the Separation of Epimeric and Positionally Isomeric Triterpenoids by Reversed Phase High Performance Liquid Chromatography

The chromatographic behavior of 8 lanostanoid triterpenes including 4 pairs of C-3 epimers and 2 pairs of C-3/C-15 positional isomers was studied by reversed phase HPLC. A consistent elution sequence of these paired isomers in all combination of three distinct solvent systems was observed. The mobile phase selectivity to separate specific, paired isomers was mainly dependent on the polarity difference contributed by C-3/C-15 hydroxyl and acetoxyl groups. The stereochemistry at C-3 played more profound role in guiding the hydrophobic interaction with C₁₈ stationary phase in the separation of C-3/C-15 positional isomers.     

ENERGY TRANSFER AND CYTOCHROME FUNCTION IN A NEW TYPE OF PHOTOSYNTHETIC BACTERIUM*

Abstract— The excitation spectrum for bacteriochlorophyll b fluorescence at 1027 mμ in Rhodopseudomonas sp. NHTC 133 indicates that the efficiency of energy transfer from caro-tenoid to bacteriochlorophyll b is between 27 and 28 %.
Light-induced absorbancy changes in anaerobic whole cells indicated the oxidation of three c -type cytochromes (C-550. 5, C-553, C-558) and one b -type cytochrome or cytochromoid C (C-560). At low light intensities C-553 is the main cytochrome oxidized, while at high light intensities mainly C-558 is oxidized in addition to C-553. The light responses of the heme proteins appear to be similar to those observed previously in purple and green photo-synthetic bacteria. No light-induced shifts in carotenoid absorption bands were detected.
In bacterial extracts C-553 and C-558 are bound to the chromatophores, while C-550. 5 is soluble.     

Muricatenol, a Linear Acetogenin from Annona muricata (Annonaceae)

Annonaceous acetogenins (polyketides) are a group of extensively investigated naturalcompounds possessing antitumor, antiparasitic and pesticidal activities. Over 350acetogenins have been isolated and most of them have one to three tetrahydrofuran (THF)cores, several hydroxyls and a terminal y-lactone ring. As part of our investigation ofthe title species, we have reported four new C,, acetogeninst muricatalin',muricatalicin=, annonacin-B' and murihexol 2' and four known acetogenins4 annonac…     

Fragmentation of dipyridamole and related dipyrimidines by electrospray ionization collisional activated decomposition mass spectrometry

The coronary vasodilator, co-activator of antitumor compounds and antioxidant drug dipyridamole and several of its derivatives were studied by electrospray ionization (ESI) combined with collisional activated decomposition (CAD) in both positive and negative modes. These compounds produce abundant monocharged ions ([M + H](+)) under ESI. Interpretation of the CAD spectra showed that fragmentation occurs preferentially in the ethanolamine groups attached at C-2, C-4, C-6 and C-8. 2-Methoxyethanol is eliminated when ethanolamines are in positions C-2/C-6 and 2-aziridinethanol is eliminated from C-4/C-8 ethanolamines. The proposed fragmentation schemes were supported by deuterium labeling experiments and tandem mass spectrometry.     

Xanthone in synthesis: a reactivity profile via directed lithiation of its dimethyl ketal

Xanthone, as its dimethyl ketal, undergoes functionalization with a synthetically useful degree of regioselectivity using a lithiation protocol. The core structure is regenerated during the work-up. Monosubstitution at C-4 or C-1 and disubstitution at C-4 and C-5 or C-1 and C-5 are observed. The substitution pattern appears to be dependent upon the experimental conditions.     

Derivatives and reactions of glutacondialdehyde V : The crystal and molecular structure of 5-hydroxy-trans-2, trans-4-pentadienal acetate. The charge distribution in the glutacondialdehyde anion

The structure of 5-hydroxy-trans-2, trans-4-pentadienal acetate has been determined, using three-dimensional diffractometercollected X-ray data. The compound has the all-trans configuration with the atoms C-1 to C-5 in a plane. The charge distribution in the acetate and in the glutacondialdehyde anion have been calculated using the CNDO/2 approximation. In both compounds higher negative charges were found on carbon atoms C-2 and C-4 than on C-1, C-3 and C-5.     

Assignment of the liposidomycin diazepanone stereochemistry

The liposidomycins comprise a family of complex nucleoside antibiotics that inhibit bacterial peptidoglycan synthesis. Their structures (1, 2) feature nucleoside, ribofuranoside, diazepanone, and lipid regions. Several stereogenic centers remain unassigned, including three within the diazepanone region: C-6', C-2'", and C-3'". An intramolecular reductive amination reaction has been used to prepare model diazepanones. Analysis of 40 and two of its diastereomers by NMR spectroscopy, X-ray crystallography, and molecular modeling indicates a close relative configurational and conformational match between 40 and the liposidomycin diazepanone degradation product 43 and allows the assignment of stereochemistry of the natural products as either [C-6'(R), C-2'"(R), C-3'"(R)] or [C-6'(S), C-2'"(S), C-3'"(S)].     

Les spectres de masse dans l' analyse 10e communication [1] les transferts d'hygrogène dans des cétones norbornyliques

Some simple rules for predicting the transfer of endo hydrogens in the mass spectra of norbornane carbonyl derivatives are proposed. Transfers from C-6 to C-2 generally occur, but are repressed if a methyl group is on C-1. Transfers from C-5 to C-2 can occur, but are less favorable than 1-3 transfers. Endo-2-acetylnorbornanes undergo a γ-hydrogen transfer from C-5 with ring fission.     

Antibiotika aus actinomyceten. zur stereochemie der griseorhodine

On the basis of chemical reactions, ¹H-NMR-studies, and model inspections the configurations of the antibiotics griseorhodin A and griseorhodin C have been determined as follows: griseorhodin A C-3'(R), C-2/2' (S), C-3 (R), C-4 (R) or its enantiomer, griseorhodin C C-3' (R), C-2/2' (S), C-3 (R), C-4 (S) or its enantiomer.