ABSTRACT
We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.
Subject(s)
Carbon , Heterocyclic Compounds, 4 or More Rings , Stereoisomerism , Cyclization , Heterocyclic Compounds, 4 or More Rings/chemistryABSTRACT
A stereoselective construction of the methylcyclopentane core (3) of jatrophane diterpenoids peditithins B-H was achieved in 14 steps from commercially available d-(+)-ribono-1,4-lactone (9). The linear 5-ene-heptanal derived from 9 was cyclized to the five-membered ring by an intramolecular carbonyl ene reaction, and five continuous stereocenters on 3 were stereoselectively introduced via a successive substrate-controlled manner, involving diastereoselective 1,4-addition, MoOPH-induced hydroxylation, and stereospecific epoxidation.
ABSTRACT
The phytochemical investigation of the roots of Croton crassifolius led to the isolation of 16 new halimane furanoditerpenoids, crohalifuranes A-P (1-16), along with 15 known analogues, 17-31. The new structures including their absolute configurations were elucidated by NMR and MS data analysis, comparison of experimental and calculated electronic circular dichroism data, single-crystal X-ray diffraction data, and chemical methods. Crohalifuranes A (1) and B (2) are tetranor- and 19-nor-halimane diterpenoids featuring a rare decahydroacenaphthene core, respectively, which might be derived from the accompanying crassifoliusin A by loss of the furan ring or the C-19 substituent. Crohalifurane C (3) represents the first example of a 20-nor-halimane diterpenoid, and crohalifurane D (4) is characterized by an unusual 6,20-δ-lactone moiety. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and 2 and 23 exhibited moderate inhibition on NO production with IC50 values of 17.2 ± 1.3 and 23.7 ± 1.4 µM, respectively.
Subject(s)
Croton/chemistry , Diterpenes, Clerodane/chemistry , Diterpenes/chemistry , Lipopolysaccharides/chemistry , Nitric Oxide/analysis , Plant Roots/chemistry , RAW 264.7 Cells/chemistry , Animals , Circular Dichroism , Crystallography, X-Ray , Diterpenes/isolation & purification , Diterpenes, Clerodane/isolation & purification , Furans/chemistry , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Nitric Oxide/chemistryABSTRACT
Phytochemical investigation on the leaves and twigs of Toona ciliata has led to the isolation of four new polyynes (1-4) and two knowns (5 and 6). Their structures were determined by extensive spectroscopic analysis (MS, UV, IR, and NMR) and Mosher's method. All compounds were evaluated for their inhibitory activities against HepG2 human tumor cell line but were inactive.
Subject(s)
Meliaceae/chemistry , Polyynes/isolation & purification , Cell Line, Tumor , Hep G2 Cells/drug effects , Humans , Molecular Structure , Plant Leaves/chemistry , Plant Stems/chemistry , Polyynes/chemistry , Polyynes/pharmacology , Spectrum AnalysisABSTRACT
A germacrane sesquiterpenoid library containing 30 compounds (2-31) was constructed by structural modification of a major component aristolactone (1) from the traditional Chinese medicine Aristolochia yunnanensis. Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFß/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFß type I receptor (IC50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.
