Asymmetric dihydroxylation of drim-7-en-11-ol: synthesis of diastereomerically pure driman-7α,8α,11-triol and its elaboration into novel chlorinated norlabdanic compounds

The asymmetric dihydroxylation of drim-7-en-11-ol was studied in detail and diastereomerically pure driman-7α,8α,11- and driman-7β,8β,11-triols were prepared. Further elaboration of driman-7α,8α,11-triol afforded 14,15-bisnorlabd-7α,8α-isopropylidenedioxy-11,13-dione from which a novel chlorinated bisnorlabdanic compound (14,15-bisnorlabd-12-ene-12-chloro-8α,13-epoxy-7α-ol-11-one) and an unusual dichloro-derivative, 13,14,15,16-tetranorlabd-12-dichloro-7α-acetoxy-8α-ol-11-one, were obtained.     

Synthesis of Drim-7,9(11)-diene and Its Hydroxylated Derivatives

This article describes a new efficient synthesis of drim-7,9(11)-diene and its hydroxylated derivates from drim-8-en-7-one. Reduction of this ketone with NaBO₄ in the presence of CeCl₃ · 7H₂O afforded regio- and stereoselectively drim-8-en-7β-ol in a high yield. Its dehydration with H₂SO₄ under mild conditions led to drim-7,9(11)-diene. Noncatalytic oxidation of drim-7,9(11)-diene with OsO₄ and the catalytic oxidation with the pair OsO₄–NMO gave, in a high yield, depending on conditions, driman-7β,8β,9α,11-tetraol or its mixture with drim-7-en-9α,11-diol and drim-9(11)-en-7α,8α-diol. Under optimal conditions the total yield of these diols reached 89%. The separate, noncatalytic oxidation of drim-7-en-9α,11-diol and of drim-9(11)-en-7α,8α-diol with OsO₄ afforded driman-7α,8α,9α,11-tetraol.     

Three new sesquiterpenes from the black heartwood of Cryptomeria japonica

Three new sesquiterpenes, (4S)-2,6,10-bisaboratrien-4-ol-1-one (1), 1,8-epoxy-1(6),2,4,7,10-bisaborapenta-en-4-ol (2), and 1-methoxy-4-cadinene (3) have been isolated from the black heartwood of Cryptomeria japonica. Compounds 1 and 2 were designated sugikurojinols A and B, respectively, and the structures of compounds 1-3 were established by extensive NMR experiments. Compounds 1 and 2 were also examined for antibacterial activity against Staphylococcus aureus and Escherichia coli, and for termiticidal activity against Coptotermes formosanus SHIRAKI.     

Physical constraints on sesquiterpene diversity arising from cyclization of the eudesm-5-yl carbocation

The biogenic origins of complex cyclic terpenes derive from the interplay of enzymes and the intrinsic reactivity of carbocation species at major branch-points along intramolecular cyclization pathways to ultimately determine the distribution of terpene skeletal types in nature. Solanaceous plants biosynthesize chemical defense compounds, largely derived from the eremophilane and spirovetivane-type sesquiterpenes. These hydrocarbon skeletons share a common biogenic origin, stemming from alternative Wagner-Meerwein rearrangements of the eudesm-5-yl carbocation during the cyclization of farnesyl pyrophosphate (FPP) catalyzed by sesquiterpene synthases. While the spirojatamane skeleton shares the same carbocation intermediate, this class of sesquiterpenes has not been reported in the Solanaceae and is exceedingly rare in nature. To investigate the physical basis for alternative rearrangements of the eudesm-5-yl carbocation, we carried out quantum mechanics (QM) analyses to calculate the allowable conformations, energies, and transition states linking conformers of the eudesm-5-yl carbocation to the eremophilene, spirovetivane, and spirojatamane skeletons. Additionally, we conducted parallel investigations on simplified decalin carbocation systems to examine the contribution of ring substituents to allowable conformations and rearrangement pathways. Our study reveals that ring substituents expand the conformational space accessible to the eudesm-5-yl carbocation while sterically blocking rearrangements in certain contexts. From our analysis, we define a conformational threshold for each possible rearrangement based on dihedral angles describing transition state geometry. Further, our calculations indicate that methylene migration rearrangements leading to spiro compounds are thermodynamically dominant in the eudesm-5-yl and simpler decalin carabocation systems. Interestingly, the theoretical abundance of sesquiterpene skeletal types arising from the intrinsic reactivity of the eudesm-5-yl carbocation stands in sharp contrast to their currently known natural abundance. The implications of these results for the catalytic tragectories catalyzed by sesquiterpene synthases are discussed.     

Chemical constituents of Blumea balsamifera of Indonesia and their protein tyrosine phosphatase 1B inhibitory activity

A methanol extract of the leaves of Blumea balsamifera (L.) DC. (Asteraceae) afforded a new guaian-type sesquiterpene, epiblumeaene K (1), together with four known guaian-type sesquiterpenes (2-5), three known sesquiterpenes (6-8), and nine known flavonoids (9-17) by a combination of chromatography and preparative TLC techniques. Their structures were elucidated by extensive spectroscopic methods and comparison with the literature data. Among the isolated compounds, a known sesquiterpene, beta-caryophyllene 8R,9R-oxide (6), exhibited a significant PTP1B inhibitory activity in a dose-dependent manner, with an IC50 value of 25.8 microM (5.62 microg/mL).     

Terpenoids—LXXVI: Precapnelladiene,a possible biosynthetic precursor of the capnellane skeleton

A new sesquiterpene hydrocarbon, precapnelladiene (I) which does not obey the isoprene rule, was isolated from the nonpolar fractions of the soft coral Capnella imbricata. Its structure was established by chemical as well as spectral evidence, with additional aid of the CONGEN computer program. Precapnelladiene has a fused 5- and 8-membered ring system and may be a biogenetic precursor of the unique tricyclic capnellane skeleton typical of sesquiterpenes isolated from the same marine animal.     

New humulane-type sesquiterpenes from the liverworts Tylimanthus tenellus and Marchantia emarginata subsp. tosana

The ether extract of the New Zealand liverwort Tylimanthus tenellus produced three new sesquiterpenes, together with (+)-3,11-eudesmadiene and (-)-4(15),11-eudesmadiene which were enantiomeric to those isolated from higher plants. The structures of the new sesquiterpenes were established by 2D NMR spectral data and/or X-ray crystallographic analysis. Those structures were shown to be humulane type sesquiterpene alcohol, and its esters of 2,4-hexadienedioic acid 3,4-dihydroxy-2,5-diphenyl-gamma-lactone. 1,6-Humuladien-10-ol was also isolated from Japanese liverwort Marchantia emarginata subsp. tosana. The absolute configuration of 1,6-humuladien-10-ol was determined by (1)H-NMR resolution of its diastereomeric methoxy-alpha-trifluoromethylphenylacetyl (MTPA) esters. It was shown to be (3S,10R)-1,6-humuladien-10-ol.     

New sesquiterpenes from Euonymus europaeus (Celastraceae)

A new sesquiterpene evoninate alkaloid (1), and two sesquiterpenes (2, 3) with a dihydro-beta-agarofuran skeleton, along with three known sesquiterpenes (4-6), were isolated from the seeds of Euonymus europaeus. Their structures were elucidated by high resolution mass analysis, and one- and two-dimensional (1D and 2D) NMR spectroscopy, including homonuclear and heteronuclear correlation [correlation spectroscopy (COSY), rotating frame Overhauser enhancement spectroscopy (ROESY), heteronuclear single quantum coherence (HSQC), and heteronuclear multiple bond correlation (HMBC)] experiments.     

Phytoquinoids and Secoprezizaane‐Type Sesquiterpenes from Illicium arborescens

A phytochemical investigation of the MeOH extract of Illicium arborescens yielded the two new phytoquinoid epimers, 2,3‐didehydro‐5‐O‐methyl‐11‐epiillifunone E ( 1 ) and 2,3‐didehydro‐5‐O‐methylillifunone E ( 2 ), as well as five new sesquiterpene lactones (8,9‐secoprezizaane‐type sesquiterpenes). Two of them, i.e., 3 and 4 , were minwanensin‐type sesquiterpenes, the other two, i.e., 5 and 6 , had the anisatin‐type (or floridanolide type) skeleton, and the fifth, i.e., 7 , was a dunnianin‐type sesquiterpene. Their structures were established by analyses of 1D‐ and 2D‐NMR, HR‐MS, and chemical evidence. The in vitro cytotoxic activity of compounds 1 – 7 was tested against four human tumor cell lines, including HeLa (cervical epitheloid), WiDr (colon), Daoy (medulloblastoma), and Hep2 (liver carcinoma) human‐tumor cells.     

Novel sesquiterpenes and a lactone from the Jamaican sponge Myrmekioderma styx

Two novel sesquiterpenes, styxone A (1) and styxone B (2), and a novel lactone, styxlactone (3), were isolated from the Jamaican sponge Myrmekioderma styx. Their structures were elucidated by detailed ¹H, ¹³C and 2D NMR data and the absolute stereochemistry of styxone A and B was determined by CD spectra. Styxone A represents a novel sesquiterpene skeleton. (S)-(+)-Curcuphenol (4), (S)-(+)-curcudiol (5), and abolene (6) were also isolated. An activity enhancement by cyanthiwigin B (7) to curcuphenol was observed in the antimicrobial assays when the two compounds were administered together.     

Synthesis and structural revision of (+/-)-laurentristich-4-ol

The structure of tetracyclic natural sesquiterpene laurentristich-4-ol was revised based on its synthetic studies. The proposed and the revised structures of laurentristich-4-ol were both synthesized with SmI(2)-mediated ketyl radical cyclization as the key step to construct the spirocyclic ether skeleton.     

Medicinal foodstuffs. XXVIII. Inhibitors of nitric oxide production and new sesquiterpenes, zedoarofuran, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, from Zedoariae Rhizoma.

A new eudesmane-type sesquiterpene, zedoarofuran, and six new guaiane- or seco-guaiane-type sesquiterpenes, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, were isolated from aqueous acetone extract of Zedoariae Rhizoma together with 36 known sesquiterpenes and two diarylheptanoids. Their stereostructures were elucidated on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages were examined and 16 sesquiterpenes including gajutsulactones A and B, and bis(4-hydroxycinnamoyl)methane were found to show inhibitory activity.     

气相色谱保留参数用于刺五加果挥发油中萜烯及萜烯氧化物的分类

根据刺五加挥发油中24个挥发性成分在5个程序升温条件下的保留时间,采用基于Levenberg-Marquardt法的软件GC_AB计算得到相应成分的气相色谱保留参数(A, B值)。通过对其中的萜烯及萜烯氧化物之间A, B关系的相关性分析,发现相同碳数的单萜烯、倍半萜烯和其氧化物分别具有良好的A-B线性相关性,但单萜烯与倍半萜烯、单萜烯与其氧化物、倍半萜烯与其氧化物的A-B关系不共线。研究表明,在中草药挥发油之类的复杂未知混合物体系的分析中,通过色谱保留参数进行萜烯及萜烯氧化物的分类是一种很有潜力的辅助定性方法。     

Constituents of south Indian vetiver oils

The essential oils isolated from vetiver [Vetiveria zizanioides (L.) Nash.] roots collected from four locations in south India were analyzed by GC-FID and GC-MS. Eighty constituents, representing 94.5-97.8% of the oils, have been identified. The oils from Bangalore, Hyderabad, Kundapur, and Mettupalayam were rich in sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The main components of the four essential oils were: eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9-6.1%), beta-vetivenene (0.9-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6-6.9%). The important compounds that impart the characteristic vetiver odor are: khusimene, delta-selinene, beta-vetivenene, cyclocopacamphan-12-ol (epimers A and B), vetiselinenol, khusimol, isovalencenol, khusimone, alpha-vetivone, and beta-vetivone. The chemical profiles of the oils are comparable to Haitian vetiver oil.     

A New Eremophilane Sesquiterpene from Cultures of the Fungus Pholiota nameko

Chemistry of Natural Compounds - A new eremophilane sesquiterpene (1), together with four known sesquiterpenes, donacinol B (2), donacinol C (3), trichapargin A (4), and trichapargin B (5), were...     

Expedient Synthesis of (R)-Patulolide A

An efficient derivation of the title compound has been formulated from easily accessible 10-undecenoic acid (1). Thus, dodec-11-en-2-ol (3), prepared from 1, was pyranylated and subjected to bromination with NBS followed by acetolysis to furnish (2E)-1-acetoxy-11-(tetrahydropyranyloxy)dodec-2-ene (5). Its hydrolysis, oxidation, and depyranylation afforded the (2E)-hydroxy ester (9). This, on Candida rugosa lipase-catalyzed acetylation, SeO(2) oxidation, hydrolysis, and Yamaguchi macrolactonization, led to (R)-patulolide A (I) with 67.1% ee. The enantiomeric excess was improved to 97% by first resolving the alcohol 3 via porcine pancreatic lipase catalyzed acetylation and converting the corresponding (R)-acetate (13) to I as done above.     

Antibacterial sphingolipid and steroids from the black coral Antipathes dichotoma

From the black coral Antipathies dichotoma, a sphingolipid (2S*,3S*,4E,8E)-2N-[tetradecanoyl]-4(E),8(E)-icosadiene-1,3-diol (1) and a steroid (22E)-methylcholesta-5,22-diene-1α,3β,7α-triol (2) were isolated. Other known compounds, 3β,7α-dihydroxy-cholest-5-ene (3), (22E,24S),5α,8α-epidioxy-24-methylcholesta-6,22-dien-3β-ol (4) and (22E,24S),5α,8α-epidioxy-24-methylcholesta-6,9(11),22-trien-3β-ol (5). The structures were established on the basis of NMR spectroscopic analysis and comparison with literature. The antibacterial activity of five compounds was evaluated.     

(E)-2,6,10-Trimethyldodec-8-en-2-ol: An Undescribed Sesquiterpenoid from Copaiba Oil

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil.     

Accelerating Biphasic Biocatalysis through New Process Windows

Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high‐performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase‐transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase‐catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high‐value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions.     

Sesquiterpene constituents of the liverwort Lophozia ventricosa

The essential oil of Lophozia ventricosa was investigated and yielded the two new sesquiterpenoids ventricos-7(13)-ene and 6,7-epoxyeudesm-3-ene. The first has a new skeleton, which is named ventricosane and is numbered after the structurally closest known sesquiterpene skeleton pentalenane. The absolute configuration of the latter compound was established by conversion to known compounds. The isolated compounds and reaction products were investigated using enantioselective GC and extensive NMR measurements (¹H; ¹H–¹H COSY; HSQC; HMBC and NOE experiments).