Regio- and stereoselectivity in the coupling reaction of secologanin with dopamine derivatives

The coupling reaction of tetraacetylsecologanin with dopamine and its N-benzyl derivative was investigated. In both series, stereoisomers at C-1, as well as regioisomer normal and neo compounds, were formed. Moreover, the N-unsubstituted products were partially lactamized, and the N-benzyl derivatives epimerized at C-1. In the products, the R configuration of C-1 over the S and the formation of the normal structure over the neo one predominated. The epimerization of both epimers gave an equilibrium of R and S in a ratio of 7:3 and was interpreted by cleavage of the C-1-N-2 bond. The fact that lactamization was much faster in the R than in the S series was explained on the basis of the supposed transition states. The structure, the configuration of C-1, and in several cases the conformations were established by detailed NMR studies and supported by chemical correlations.     

Investigation of Pictet-Spengler type reactions of secologanin with histamine and its benzyl derivative

The reaction of secologanin (1) (mainly in its tetraacetylated form 1a) with histamine (2) and its benzyl derivative (2b) was investigated. With the benzylated amine (2b), the main product was the normal, tetraacetylated benzyl derivative of histeloside having the R configuration at the new center of chirality, C-1 (5b), with a small amount of an unidentified minor component (probably the 1S epimer 5a). In a slightly acidic medium, the reaction with histamine (2) gave two products in an approximately 6:4 ratio. The main compound proved to be the normal, tetraacetylated derivative of the lactam histelosamide with R configuration at C-1 (7b), and the minor product was the tetraacetylisohisteloside with S configuration at the same C-1 center (3a). When the reaction was carried out under acid-free conditions, in addition to the epimeric pair of the normal tetraacetylated lactam (7a, 7b) and the tetraacetylisohisteloside with 1S configuration (3a), tetraacetylneohistelosamide (8b) was also isolated, in which the cyclization took place at one of the cyclic nitrogens of the imidazole ring. Probably, this latter compound is an intermediate also in the formation of the normal isomers, but under slightly acidic conditions it rapidly isomerized into the normal alkaloid. The tendencies experienced previously in the tryptamine and dopamine series were observed also in the histamine series; that is, at C-1, the R configuration is favored over the S one, and lactamization is faster in the former than in the latter case. The structure of the products and their stereoschemistry were established by NMR spectroscopy.     

Synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acid

The stereospecific synthesis of (7S,15S)- and (7R,15S)-dolatrienoic acids (2) was achieved using an approach consisting of 16 linear steps. The C-11--C-16 unit was prepared in seven steps from ethyl (S)-lactate and coupled using a trans-selective Wittig--Schlosser reaction to the C-7--C-10 fragment. Chirality at the C-7 position was introduced using an Evan's-type chiral auxiliary in a cobalt-mediated Reformatsky reaction to give the (3S,11S)-aldehyde 24. Subsequent Wittig reaction with a phosphonium salt derived in three steps from tiglic acid gave (7S,15S)-dolatrienoic acid, one of the four possible diastereoisomers of the nonpeptide portion of the strong cancer cell growth inhibitory cyclodepsipeptide dolastatin 14 (1). A second diastereoisomer, (7R,15S)-dolatrienoic acid, was synthesized employing chiral oxazolidinone 21 by an analogous synthetic route.     

Secondary metabolites from the roots of Astragalus trojanus

Six novel cycloartane-type glycosides were isolated from the roots of Astragalus trojanus. Two of these, compounds 1 and 2, have (20R, 24S)-epoxy-3beta,6alpha,16beta,25-tetrahydroxycycloartane as the aglycon, while compounds 3-6 possess 3beta,6alpha,16beta,(24S), 25-pentahydroxycycloartane as the aglycon. The saccharide moieties linked to the C-3, C-6, and C-24 or C-25 positions of the aglycons in 1-6 contained either xylopyranose, glucopyranose, rhamnopyranose, or arabinopyranose units. Structure elucidation of compounds 1-6 was accomplished through the extensive use of 1D and 2D NMR techniques. In addition, a new oleanene glycoside (7) and a new tryptophan derivative (8) were also isolated and characterized.     

Paratunamides A-D, oxindole alkaloids from Cinnamodendron axillare

Four new oxindole alkaloids, paratunamides A-D (1-4), containing a secologanin unit, were isolated from the bark of Cinnamodendron axillare, and their structures and relative configurations were elucidated by spectroscopic data. The absolute configuration at C-7 in 1-4 was assigned as S, S, R, and S, respectively, on the basis of the CD spectra.     

An approach to furolabdanes and their photooxidation derivatives from R-(+)-sclareolide

A synthetic route to furolabdanes from commercially available R-(+)-sclareolide is reported, with the specific aim of preparing (12R and 12S,15xi)-12,15-dihydroxylabda-7,13-dien-16,15-olides (3 and 5) and (12R and 12S,16xi)-12,16-dihydroxylabda-7,13-dien-15,16-olides (4 and 6). The key points of our approach are the use of Weinreb's amide 11 to join the furan ring to the terpenic unit. Photooxidation of the furan moiety of compounds 15 and 16, and of their acetates 19 and 20, has been used to built the hydroxybutenolide fragment. In this way the four possible isomers at the butenolide moiety, compounds 3-6, and their C-12 acetyl derivatives 21-24 have been obtained. On the basis of comparison of the spectral data ((1)H NMR) of the synthetic peracetates 25-28 (derived from 21-24) with the reported data for the peracetate 2 (derived from the natural product 1), the relative configuration at carbon C-12 of the natural product has been corrected. Furthermore, the absolute configuration of the natural product 1, considered to belong to the enantio-series, has to be changed to the normal-series on the basis of the optical rotation obtained for the synthetic derivative.     

轮叶棘豆的化学成分研究

目的：研究轮叶棘豆的化学成分。方法：90%乙醇冷浸提取,所得浸膏经硅胶,聚酰胺,C-18,Sephadex LH-20等多种材料进行柱色谱分离,通过波谱学方法鉴定化合物的结构。结果：分离鉴定了8个化合物,分别鉴定为azukisapogenol(1),(22E,24R)-24-甲基-5α-胆甾-7,22-二烯-3β,5α,6β-三醇(2),芹菜素(3),3′,4′-二甲氧基-槲皮素-3-O-β-D-半乳糖吡喃苷 (4),7,4′- 二甲氧基-槲皮素-3-O-α-L-鼠李糖吡喃基(1→2)-β-D-葡萄糖吡喃苷(5),(2S,3S,4R)-N-［(R)-2′-羟基二十四烷醇基］-1,3,4-三羟基-2-氨基-十八-6-烯(6),β-谷甾醇(7),胡萝卜苷(8)。结论：所有化合物均为首次从该植物中分得。     

Isolation and characterization of miscellaneous secondary metabolites of Deprea subtriflora

Two new C-18 norwithanolides based on a C(27) skeleton, subtrifloralactones K (1) and L (2), a new C-18 oxygenated withanolide, 13 beta-hydroxymethylsubtrifloralactone E (3), and a new alpha-ionone derivative, (+)-7 alpha,8 alpha-epoxyblumenol B (4), along with five known compounds, philadelphicalactone A (5), (2S,3S,4R)-2-[(2R)-2'-hydroxytetracosanoylamino]-1,3,4-octadecanetriol (6), trans-N-feruloyltyramine, cis-N-feruloyltyramine, and (S)-coriolic acid, were isolated from additional active fractions of the chloroform-soluble extract of Deprea subtriflora, using a quinone reductase (QR) induction assay as a monitor. The structures of compounds 1-4 were characterized by spectroscopic data interpretation. The potential cancer chemopreventive activities of all isolates in terms of their ability to induce QR activity with cultured Hepa 1c1c7 mouse hepatoma cells were evaluated.     

Absolute configuration of (-)-gambogic acid, an antitumor agent

(-)-Gambogic acid (1), a biologically active "caged xanthone" from gamboge, the dried resin of Garcinia hanburyi, is of interest as a potential anticancer agent. The planar structure of (-)-gambogic acid has been determined previously by analysis of its detailed NMR data and confirmed by single-crystal X-ray diffraction, with the absolute configuration at C-13 deduced as R through a series of chemical degradations. Using (-)-morellic acid (2), an analogue of (-)-gambogic acid, as a model compound, the 5R, 7S, 10aS, 13R, 27S absolute configuration of (-)-gambogic acid was determined for the first time by comparison of physical and spectroscopic data, especially experimental and calculated electronic circular dichroism.     

Sesquiterpene esters of aristolochic acid from the root and stem of Aristolochia heterophylla

Three novel sesquiterpene esters of aristolochic acid, aristoloterpenate-II (2), -III (3), and-IV (4), together with known aristoloterpenate-I (1), were isolated and characterized from the root and stem of Aristolochia heterophylla. Their structures were elucidated by spectroscopic methods. The absolute configuration of these compounds at C-4' was determined as R by circular dichroic studies. These compounds showed cytotoxicity against hepatoma G2, 2, 2, 15 cells.     

(2S,3S)-sulfated pterosin C, a cytotoxic sesquiterpene from the Bangladeshi mangrove fern Acrostichum aureum

Two new sesquiterpenes, (2R,3S)-sulfated pterosin C (1) and (2S,3S)-sulfated pterosin C (2), along with two known derivatives, (2S,3S)-pterosin C and (2R)-pterosin P, were isolated from a methanolic extract of the aerial parts of Acrostichum aureum. The structures of 1 and 2 were determined by the interpretation of their spectroscopic data. The isolated pterosins were evaluated for their cytotoxic activity against the AGS, HT-29, MDA-MB-231, and MCF-7 human cancer cell lines and the NIH3T3 normal mouse fibroblast cell line, using the MTT assay. Compound 2 showed IC50 values in the range 23.9-68.8 μM. The lowest IC50 value (23.9 μM) was recorded against AGS gastric adenocarcinoma cells. Compound 2 was found to exert an apoptotic effect on AGS cells within 24 h of treatment, which increased with time and was greater than the positive control, cycloheximide. The cytotoxicity of 2 seems to be due in part to the sulfate group on C-14 and the configuration at C-2.     

Improved antitumor activity by modification of nogalamycin

Nogalamycin, an antitumor antibiotic, has been converted to a series of analogs by removal of the carbomethoxy group at C-10 and replacement of the neutral sugar at C-7 by other groups. Removal of the carbomethoxy group to give disnogamycin (6) followed by acidic alcoholysis gave pairs of isomeric 7-alkoxy compounds differing in configuration at C-7. Treatment of 6 with trifluoroacetic acid followed by nucleophiles gave a series of analogs having substituents at C-7 with a configuration at C-7 opposite to that of nogalamycin. Among the analogs prepared, 7-con-O-methylnogarol (7) is a highly active antitumor agent.     

Ferruginenes A-C from Rhododendron ferrugineum and their cytotoxic evaluation

Three new compounds, ferruginenes A (1) and B (2) and a mixture of C-5'(R) and C-5'(S) ferruginene C (3) diastereomers, have been isolated from a cytotoxic chloroform-soluble fraction of the leaves of Rhododendron ferrugineum together with 12 known compounds. The structures of these new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometric data. Compounds 1-3 were tested for their cytotoxicity against three human cancer cell lines, namely, HL-60, HeLa-S3, and MCF-7.     

Cadinane sesquiterpenes from the brown alga Dictyopteris divaricata

Seven new cadinane sesquiterpenes, (-)-(1R,6S,7S,10R)-1-hydroxycadinan-3-en-5-one (1), (+)-(1R,5S,6R,7S, 10R)-cadinan-3-ene-1,5-diol (2), (+)-(1R,5R,6R,7S,10R)-cadinan-3-ene-1,5-diol (3), (+)-(1R,5S,6R,7S,10R)-cadinan-4(11)-ene-1,5-diol (4), (+)-(1R,5R,6R,7R,10R)-cadinan-4(11)-ene-1,5,12-triol (5), (-)-(1R,4R,5S,6R,7S, 10R)-cadinan-1,4,5-triol (6), and (-)-(1R,6R,7S,10R)-11-oxocadinan-4-en-1-ol (7), together with nine known compounds were isolated from the brown alga Dictyopteris divaricata. The structures of the new natural products, as well as their absolute configuration, were established by means of spectroscopic data including IR, HRMS, 1D and 2D NMR, single-crystal X-ray diffraction, and CD. All compounds were inactive against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.     

Sesquiterpenes from Blumea balsamifera

Five new guaiane sesquiterpenes, blumeaenes E1 (1), E2 (2), K (3), L (4), and M (5), and one new eudesmane sesquiterpene, samboginone (6), along with three known compounds, cryptomeridiol, 3,3',5,7-tetrahydroxy-4'-methoxyflavanone, and austroinulin, were isolated from the leaves of the Philippine medicinal herb sambong, Blumea balsamifera. The absolute configuration of the new guaiane core was determined as 1S,7S,9S,10R by employing the modified Mosher's method. In the structure of 1, the absolute configuration of the epoxyangelic acid moiety was identified as 2S,3S using (R)-PGME as a chiral anisotropic auxiliary.     

Constituents from the leaves of Phellodendron amurense var. wilsonii and their bioactivity

Two new dihydroflavonols, phellodensin-A (1) and phellodensin-C (2); three new coumarins, phellodenol-A (3), phellodenol-B (4), and phellodenol-C (5); one new chlorophyll, phellophyll-a (6); and one new phenyllactate, (2R)-sodium 3-phenyllactate (7), in addition to 35 known compounds have been isolated from the leaves of Phellodendron amurense var. wilsonii. The structures of the new compounds were established based on 1D, 2D NMR and mass spectral analyses. The stereochemistry at the C-2, C-3, and C-2' ' positions of new dihydroflavonol 1 was determined by CD spectroscopy. The known compounds were identified by comparison with authentic samples. The antioxidant and antityrosinase activities were also described.     

Preparation, stereochemical study and evaluation of the antileukemic activity of glucoside derivatives of (-)-steganol

The optically active lignan (-)-steganol was prepared from natural (-)-steganacin by selective deacetylation and was transformed, via a three-step sequence, into the corresponding 4', 6'-O-ethylidene- and thenylidene-beta-D-glucopyranosides, 3b and 3c, respectively, which are the analogues, in the steganol series, of the podophyllotoxin derived, and clinically useful, anticancer drugs, VP16-213 and VM26. Formation of the dimeric compound distegyl ether as a minor by-product was established. Complete elucidation of all the asymmetric centres was performed with the help of high resolution 1H-nmr studies at 400 MHz, COSY experiment at 500 MHz and X-ray analysis. Contrary to the podophyllotoxin series, the glycosylation of (-)-steganol occurred with retention of configuration, and all the synthesized compounds, including distegyl ether, exhibited the starting natural R configuration at C-5.     

Enantioselective synthesis of the tetrahydrofuran lignans (-)- and (+)-magnolone

The optically pure trisubstituted 7'-oxotetrahydrofuran lignans (-)- and (+)-magnolone ( 1) were synthesized by employing stereoselective S N1 intramolecular cyclization as a key reaction. The absolute configuration of naturally occurring (-)-magnolone was determined as (7 S,8 R,8' S).     

Quirogane,prenopsane, and patzcuarane skeletons obtained by photochemically induced molecular rearrangements of longipinene derivatives

Ultraviolet irradiation of (1R,3S,4S,5S,10R,11R)-1-acetyloxy-7-oxolongipin-8-ene (6), prepared from longipinene diesters isolated from Stevia salicifolia, afforded the new quirogane (7) and prenopsane (8) derivatives, as the major products, together with the minor secondary photoproduct (1R,3R,5R,8S,11S)-1-acetyloxy-7-oxopatzcuar-9-ene (9), which possesses a novel tricyclic sesquiterpene skeleton. The stereostructures of the new compounds 7-9 were mainly determined by NMR techniques including COSY, HSQC, HMBC, and NOESY in combination with molecular modeling obtained by density functional theory calculations. A reaction mechanism accounting for the observed transformations is proposed.     

Daryamides A-C, weakly cytotoxic polyketides from a marine-derived actinomycete of the genus Streptomyces strain CNQ-085

In the course of our continuing search for new antitumor-antibiotics from marine-derived actinomycete bacteria, four new cytotoxic compounds, designated as daryamides A (1), B (2), and C (3) and (2E,4E)-7-methylocta-2,4-dienoic acid amide (4), were isolated from the culture broth of a marine-derived Streptomyces strain CNQ-085. The structures of these new compounds were assigned by detailed interpretation of spectroscopic data. The relative configuration of 1 was determined by comprehensive NMR analysis, while the absolute configuration of 1 was determined as 4S,5R using the modified Mosher method. The daryamides show weak to moderate cytotoxic activity against the human colon carcinoma cell line HCT-116 and very weak antifungal activities against Candida albicans.