Total synthesis of natural spiro-trisindole enantiomers similisines A,B and their stereoisomers

The first total synthesis of similisines A and B, a pair of unprecedented polybrominated spiro-trisindole enantiomers isolated from Laurencia similis, and their all stereoisomers had been accomplished in 6 steps from the known 5,6-dibromoindole. The described synthesis avoided any protecting-group manipulations, and the key all-carbon spirocenters were constructed via an intramolecular Friedel-Crafts cyclization. In addition, the rotamers of similisines and cytotoxic and NO production inhibitory activities of synthetic compounds were also discussed.     

Total synthesis of natural products using a desymmetrization strategy

Total syntheses of SB-203207 (1) and sphingofungin E (2) were accomplished by utilizing an asymmetric desymmetrization strategy to introduce multiple stereogenic centers into meso starting compounds in a single step. Thus, rhodium carbenoid-mediated CH insertion into 3 provided the bicyclo[3.3.0]framework 4 for 1, while organocatalyst-mediated bromolactonization of 5 afforded 6 for the synthesis of 2. Similarly, we utilized desymmetric rhodium nitrenoid-mediated aziridination reaction of 5 to obtain a key intermediate required for a total synthesis of pactamycin (29), a complex aminocyclopentitol antibiotic featuring six contiguous stereogenic centers.     

Total synthesis of aldehyde-containing Garcinia natural products isomorellin and gaudichaudione A

The natural products, isomorellin and gaudichaudione A, with a 4-oxa-tricyclo[4.3.1.0^3,7] dec-8-en-2-one scaffold were synthesized for the first time using an efficient method. The key improvement of this method was the simultaneous bisalkylation of 5,6-dihydroxyxanthone with the bulky 2-methylbutyne group. This method obviously shortened the synthetic route and enhanced the total yield. Four analogues named forbesione, desoxymorellin, desoxygaudichaudione A, and gambogin containing the same caged structure were prepared using this method.     

Chemoenzymatic total synthesis of cryptocaryalactone natural products

A new chemoenzymatic route for the preparation of cryptocaryalactones natural products using a kinetic resolution process as the key step is described. Novozyme-435 catalyzed hydrolysis of the prochiral (±)-monoester 7 afforded the precursors of cryptocaryalactones with high enantiomeric excess and excellent yields. The compounds (4S,6S)-7 and (4R,6R)-7 were converted to (+)-(6R,2′S)-cryptocaryalactone (1) and (?)-(6S,2′R)-cryptocaryalactone (2), respectively by employing Wittig-olefination, lactonization and acylation reactions.     

Total synthesis and anticancer activity studies of the stereoisomers of asperphenamate and patriscabratine

<正>All stereoisomers of asperphenamate 1a and patriscabratine 2a were achieved with a high yield,and total synthesis of 2a is firstly described here.The absolute configuration of patriscabratine was determined as(S,S).The compounds 1a-d and 2a-d have been tested by MTT assay in T47D,MDA-MB231,HL60,Hela and SGC-7901 cell lines in vitro.Among them,the(R,S) stereoisomer shows the strongest anticancer effects,while the(S,R) shows the weakest one.     

Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acids

Pinellic acid from the tuber of Pinellia ternate, an active herbal component of the traditional Japanese herbal (Kampo) medicine Sho-seiryu-to, is a C18 trihydroxy fatty acid whose absolute stereochemistry has now been determined. All stereoisomers of pinellic acid were synthesized via regioselective asymmetric dihydroxylation, regioselective inversion, and stereoselective reduction in order to determine their absolute stereochemistries and adjuvant activities. Among this series of isomers, the (9S,12S,13S)-compound, which is a natural product, exhibited the most potent adjuvant activity. Spectral data for all of the stereoisomers of the 1,2-allylic diols were compared and related to their stereochemistries.     

First total synthesis of natural products cajanolactone A and cajanonic acid A

First total synthesis of cajanolactone A and cajanonic acid A has been achieved through steps of anion–anion condensations,cyclization,Williams etherification,selective demethylation,1 3-sigmatropic rearrangement and hydrolysis.This work provides an efficient method for future cajanonic acid A derivatives synthesis.     

The conversion of methylenomycin A to natural botryodiplodin and their absolute configurations

Natural (?)-botryodiplodin($\text{1}$) has been synthesized from an antibiotic methylenomycin A ($\text{2}$). The absolute configurations of (?)-botryodiplodin($\text{1}$ and methylenomycin A ($\text{2}$) have also been established as shown in $\text{1}$ and $\text{2}$ respectively.     

Enantioselective synthesis and absolute configurations of aculeatins A and B

The two naturally occuring, bioactive spiroacetals aculeatins A and B 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 the previously assigned relative configurations have been corrected.     

Total synthesis of janadolide

The first total synthesis of janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, is described. The synthesis of an unsaturated hydroxycarboxylic acid was effected via the lithiation of vinyl iodide followed by addition to a Weinreb amide with a tert-butyl group and stereoselective 1,2-reduction. The cyclic structure was constructed by macrolactamization at the amide bond between the proline moiety and fatty acid moiety.     

Total synthesis of racemic,natural (+) and unnatural (−) scorzocreticin

The first total synthesis of racemic scorzocreticin and its pure enantiomers is described from readily available 3,5-dihydroxybenzoic acid. The key steps include Wittig olefination, asymmetric Me-CBS (Corey–Bakshi–Shibata) oxazaborolidine reduction, and improved Pd-catalyzed intramolecular lactonization reactions. Both the (S)-natural and (R)-unnatural enantiomers of scorzocreticin have been synthesized in excellent enantioselectivities (>99% and 99% ee, respectively). In addition, 1,10-phenanthroline, a bidentate N-ligand was employed in palladium-catalyzed intramolecular carbonylation/lactonization reaction for the construction of 3,4-dihydroisocoumarin ring.     

An expeditious total synthesis of kalkitoxins: determination of the absolute stereostructure of natural kalkitoxin

Kalkitoxin, a potent neurotoxin isolated from the marine cyanobacteria Lyngbya majuscula, and its congeners (1-7) were efficiently synthesized utilizing Hruby's diastereoselective 1,4-addition and the Wipf's oxazoline-thiazoline conversion as key steps. These synthetic efforts in combination with spectral studies of natural kalkitoxin clearly determined the absolute stereostructure of kalkitoxin to be 7.     

Indole synthesis by radical cyclization of o-alkenylphenyl isocyanides and its application to the total synthesis of natural products

Development of indole synthesis by tin-mediated radical cyclization of o-alkenylphenyl isocyanide is described. Upon heating o-alkenylphenyl isocyanide in the presence of tri-n-butyltin hydride and AIBN, 2-stannyl-3-substituted indole was formed via 5-exo-trig cyclization of the imidoyl radical intermediate. After acidic workup, 3-substituted indoles were isolated. For substrates bearing simple alkyl groups, a substantial amount of tetrahydroquinoline derivatives were generated through 6-endo-trig cyclization. This undesired cyclization was suppressed by using an excess amount (five equivalents based on o-alkenylphenyl isocyanide) of ethanethiol instead of tri-n-butyltin hydride. The 2-stannylindole intermediates proved to be a suitable substrate for Stille coupling, giving 2,3-disubstituted indoles in a one-pot procedure. In addition, the 2-stannylindole intermediates could be converted to 2-iodoindoles by treatment with iodine or N-iodosuccinimide. The 2-iodoindoles thus obtained served as good substrates for Heck reactions, Stille couplings, Suzuki couplings, and palladium-mediated carbonylations, to afford a variety of 2,3-disubstituted indoles. The utility of this protocol was demonstrated by application to synthetic studies on gelsemine and discorhabdin A, and the total synthesis of an aspidosperma alkaloid, (-)-vindoline.     

Total syntheses of cyclitol based natural products from myo-inositol: brahol and pinpollitol

Inositol and their derivatives are important class of biologically active natural products. Among the nine theoretically possible inositols, six are known to occur in nature. Interestingly one or more methyl ethers of these inositols have been isolated from plants and these methyl inositols are presumed to have important functions in plant biology. Brahol and pinpollitol are two naturally occurring methylated inositols reported to have allo-inositol and chiro-inositol configurations, respectively. Adopting our sulfonate inversion strategies for synthesizing protected chiro- and allo-inositols from cheaply available myo-inositol in combination with new methods we have achieved the total syntheses of these methylated inositols. The proposed structure of brahol has been synthesized in six steps from myo-inositol. We have not only disproved the proposed structure of brahol but also established its correct structure. Also, we have efficiently synthesized pinpollitol and its positional isomer from myo-inositol. These works involve several selective protection-deprotection strategies of inositol hydroxyl groups.     

First enantioselective total synthesis of (−)-dysibetaine CPa and absolute configurations of natural product

Here we report total synthesis of enantiomerically pure dysibetaine CPa, isolated from Micronesian marine sponge and expected to serve as a neuroactive agent. Starting from meso-cyclopropane triester, the synthesis was achieved in 12.8% overall yield over 10 steps including organocatalytic enantioselective solvolysis of meso-succinic anhydride as a key step. This work established the absolute configurations of the natural product as (3R,4R).