Asymmetric routes to pentadec-1-en-4-ol: application to the syntheses of aculeatins F and epi-F, (R)- and (S)-5-hexadecanolide and a formal synthesis of solenopsin

A short and simple route to the synthesis of pentadec-1-en-4-ol, an important synthetic building block for the aculeatins F and epi-F, insect pheromone 5-hexadecanolide, solenopsin and various other natural products has been developed via proline-catalyzed α-aminoxylation of an aldehyde and hydrolytic kinetic resolution of a terminal epoxide. While the synthesis of aculeatins F and epi-F has been accomplished using a PIFA promoted oxidative spirocyclization/dithiane deprotection reaction sequence and linchpin coupling as key steps, the synthesis of hexadecanolide and a formal synthesis of solenopsin was performed using ring-closing metathesis (RCM) as key step.     

Triterpene glycosides ofCaltha polypetala glycosides A,B, D,E, and F

Five individual triterpene glycosides — A, B, D, E, and F — which are hederagen-in mono- and biosides, have been isolated from the roots ofCaltha polypetala (Great Marsh Marigold), familyRanunculaceae. Glycosides E and F proved to be new compounds for which, on the basis of the results of acid and alkaline hydrolyses, methylation, methanolysis, and physicochemical methods of investigation, the following structures are proposed: E — hederagenin 3-0-D-glucopyranoside, 28-O-L-rhamnopyranoside; and F — heteragenin 28-O-[O-L-rhamnopyranosyl-(1→ 6)-D-glucopyranoside].     

Total synthesis of naturally occurring cephalosporolides E/F

A modular total synthesis of cephalosporolides E/F featuring sequential epoxide–alkyne coupling and subsequent highly regioselective gold catalyzed alkynolcycloisomerization of the resulting alkynetetrol to construct the central spiroketal core has been documented.     

Total synthesis of aculeatins A and B from (S)-malic acid

A simple convergent approach towards the total synthesis of bioactive spiroacetals aculeatins A and B is described. The key features of the synthetic strategy include a syn-stereoselective 1,3-asymmetric reduction, epoxide ring opening and oxidative spirocyclization reaction by employing (S)-malic acid as the starting material.     

Total syntheses of lindenane-type sesquiterpenoids: (±)-chloranthalactones A, B, F, (±)-9-hydroxy heterogorgiolide, and (±)-shizukanolide E

Chloranthalactones A, B, F, 9-hydroxy heterogorgiolide, and shizukanolide E are a family of natural lindenane-type sesquiterpenoids isolated mainly from chloranthaceae. A general synthetic strategy was accomplished by us for the racemic total syntheses of the five natural products. The key steps included substrate-controlled Matteson epoxidation of ketone and highly diastereoselective intramolecular Hodgson cyclopropanation to construct the challenging cis, trans-3/5/6 tricyclic skeleton, along with a methodology developed for the γ-alkylidenebutenolide ring formation.     

Enantioselective synthesis and absolute configurations of aculeatins A, B, D, and 6-epi-aculeatin D

The three naturally occurring, bioactive spiroacetals aculeatins A, B, and D, as well as the non-natural 6-epi-aculeatin D have been synthesized for the first time in enantiopure form using an asymmetric allylation as the only chirality source. A further key step was a stereoselective aldol reaction with remote induction. The absolute configurations of the natural products have been established and an erroneous structural assignment has been corrected.     

Insight into the molecular mechanism of yeast acetyl-coenzyme A carboxylase mutants F510I,N485G,I69E,E477R,and K73R resistant to soraphen A

Acetyl-coenzyme A carboxylases (ACCs) is the first committed enzyme of fatty acid synthesis pathway. The inhibition of ACC is thought to be beneficial not only for diseases related to metabolism, such as type-2 diabetes, but also for infectious disease like bacterial infection disease. Soraphen A, a potent allosteric inhibitor of BC domain of yeast ACC, exhibit lower binding affinities to several yeast ACC mutants and the corresponding drug resistance mechanisms are still unknown. We report here a theoretical study of binding of soraphen A to wild type and yeast ACC mutants (including F510I, N485G, I69E, E477R, and K73R) via molecular dynamic simulation and molecular mechanics/generalized Born surface area free energy calculations methods. The calculated binding free energies of soraphen A to yeast ACC mutants are weaker than to wild type, which is highly consistent with the experimental results. The mutant F510I weakens the binding affinity of soraphen A to yeast ACC mainly by decreasing the van der Waals contributions, while the weaker binding affinities of Soraphen A to other yeast ACC mutants including N485G, I69E, E477R, and K73R are largely attributed to the decreased net electrostatic (ΔE_ele?+?ΔG_GB) interactions. Our simulation results could provide important insights for the development of more potent ACC inhibitors.     

Stereoselective total synthesis of paecilomycin E and F and its two congeners Cochliomycin C and 6-epi-Cochliomycin C

An efficient and concise approach to the total synthesis of Paecilomycins E (1) and F (2), Cochliomycin C (4) and 6-epi-Cochliomycin C (3) is described. The synthesis involves novel route to the synthesis of Paecilomycin E and F and further conversion to Cochliomycin C and 6-epi-Cochliomycin C. Olefin metathesis and base promoted macro lactonization being the key reactions followed by chlorination to achieve target Cochliomycin C and 6-epi-Cochliomycin C.     

Total synthesis of solandelactones A, B, E, and F exploiting a tandem Petasis-Claisen lactonization strategy

Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (7 S) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C 22 oxylipins that parallels a hypothesis put forward previously to explain the origin of C 20 cyclopropane-containing algal products.     

Triterpene glycosides ofCaltha polypetala glycosides A, B, D, E, and F

Five individual triterpene glycosides — A, B, D, E, and F — which are hederagen-in mono- and biosides, have been isolated from the roots ofCaltha polypetala (Great Marsh Marigold), familyRanunculaceae. Glycosides E and F proved to be new compounds for which, on the basis of the results of acid and alkaline hydrolyses, methylation, methanolysis, and physicochemical methods of investigation, the following structures are proposed: E — hederagenin 3-0-D-glucopyranoside, 28-O-L-rhamnopyranoside; and F — heteragenin 28-O-[O-L-rhamnopyranosyl-(1 6)-D-glucopyranoside].I. G. Kutateladze Institute of Pharmacochemistry, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 712–716, November–December, 1986.     

Lissoclinotoxins E and F, novel cytotoxic alkaloids from a Philippine didemnid ascidian

Bioassay-guided fractionation of the MeOH extract from a Philippine didemnid ascidian resulted in the isolation of two new dimeric alkaloids, lissoclinotoxins E (1) and F (2). The polysulfide structures for compounds 1 and 2 were determined by interpretation of spectroscopic data and chemical degradation. Computational chemistry studies suggested that the N-alkyl chains about the tricyclic systems of lissoclinotoxins E and F had trans and cis orientations, respectively. Alkaloids 1 and 2 displayed IC₅₀ values of 2.3 and 1.5 μg/mL, respectively, towards the PTEN-deficient human breast carcinoma cell line, MDA-MB-468.     

Specific detection of Clostridium botulinum types A,B, E,and F using the polymerase chain reaction

Clostridium botulinum organisms generally produce 1 of 4 neurotoxin types (A, B, E, and F) associated with human illness. Neurotoxin type determination is important in identification of the bacterium. A polymerase chain reaction (PCR) method was developed to identify 24 h botulinal cultures as potential types A, B, E, and F neurotoxin producers as well as other clostridial species which also produce neurotoxins. Components of the PCR and amplification conditions were adjusted for optimal amplification of toxin gene target regions to enable simultaneous testing for types A, B, E, and F in separate tubes using a single thermal cycler. Each primer set was specific for its corresponding toxin type. A DNA extraction procedure was also included to remove inhibitory substances that may affect amplification. This procedure is rapid, sensitive, and specific for identification of toxigenic C. botulinum.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Tripenoid glycosides of alfalfa. VII. Medicosides E and F

Two hederagenin glycosides — medicosides E and F — have been isolated from the roots ofMedicago sativa L. (Leguminosae). Medicoside E has the structure of hederagenin 28-O-β-D-glucopyranoside 3-O-[O-β-G-glucopyranosyl-(1→3)-β-D-xylopyranoside]. Medicoside F has the structure of hederagenin 28-O-β-D-glucopyranoside 3-O-[O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside].     

The structures of pukeleimides A,B, D,E, F,and G

Structures for pukeleimides A, B, D, E, F, and G, six novel pyrrolic compounds from a shallow-water variety of the marine blue-green alga bar|Lyngbya majuscula, are proposed from spectral data.     

Calyciphyllines E and F, novel hepta- and pentacyclic alkaloids from Daphniphyllum calycinum

Two new Daphniphyllum alkaloids, calyciphyllines E (1) and F (2), have been isolated from the leaves of Daphniphyllum calycinum (Daphniphyllaceae), and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Comparison of amplified ELISA and mouse bioassay procedures for determination of botulinal toxins A, B, E, and F

The amplified enzyme-linked immunosorbent assay (amp-ELISA) was compared to the mouse bioassay for determination of botulinal neurotoxin types A, B, E, and F. Twelve different toxin-producing type A, 13 proteolytic type B, 9 nonproteolytic type B, 16 type E, 8 proteolytic type F, 5 nonproteolytic type F, and 6 nontoxigenic clostridial strains were tested. The cultures were inoculated into cooked meat medium (CMM) and tryptone-peptone-glucose-yeast extract (TPGY) medium, incubated for 5 days, and then examined for biological toxicity in mice and amp-ELISA endpoints. The amp-ELISA was less sensitive in detecting toxins produced by nonproteolytic than proteolytic strains of type B and F organisms. All of the toxin-producing strains tested were positive by the AOAC method and the amp-ELISA in either undiluted TPGY or CMM culture fluids regardless of mouse toxicity level, source, or strain. Cross-reactivity was observed between some but not all of the botulinal strains tested. None of the nontoxigenic strains were positive by the amp-ELISA. Purified botulinal toxins were also assayed using these 2 methods. The sensitivity of the amp-ELISA using purified neurotoxins was about 0.1 ng/mL for types A, B, and E and about 1.0 ng/mL for type F.     

Enantioselective total synthesis and stereochemical revision of communiols E and F

The enantioselective total synthesis of candidate structures for communiols E and F, novel bicyclic polyketides of fungal origin, was accomplished using a Lewis acid-mediated ring closure reaction of an allylsilane intermediate as the key step. Comparison of the spectral data of the synthetic materials with those of natural communiols E and F, coupled with biosynthetic considerations, led to the conclusion that the stereochemistry of communiols E and F should be (2S,5S,7R, 8S,11R)- and (5S,7R,8S,11R)-forms, respectively.     

Rastronole A,B, C,D, E,F, G und H; eine Gruppe multioxygenierter Diterpenbitterstoffe der ent-Kauran-Reihe aus Englerastrum scandens ALSTON

Rastronols A, B, C, D, E, F, G, and H, a group of multioxygenated bitter principles with ent-kaur-16-en-15-one structure from Englerastrum scandens ALSTON (Labiatae) We have isolated from the leaves of Englerastrum scandens from Kenya eight new, highly oxygenated ent-kaur-16-en-15-ones named rastronol A, B, C, D, E, F, G, and H, and determined their structures mainly by spectroscopic techniques as 1, 8, 14, 17, 20, 29, 39 , and 51 respectively.     

Total synthesis of aculeatins A and B via a tethered oxa-Michael approach

A stereocontrolled total synthesis of aculeatins A and B has been achieved in eight steps and in 15% overall yield. The key feature of this synthetic approach is the application of a Marouka allylation and tethered intramolecular oxa-Michael reaction to install the required stereocentres on the tetrahydropyran ring.