Total synthesis of leustroducsin B

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.     

Total synthesis of an antitumor antibiotic,Fostriecin (CI-920)

The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described. A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C. The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H. Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction. The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction. The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative. Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one. The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers.     

A Novel Synthesis of Ketoprofen,Important Non-Steroidal Antiinflammatory Agent

The α-propionic acid moiety in. ketoprofen is attached through Wittig Homer reaction of ethyl-phosphono propionate on 3-benzyl cyclohexanone, prepared by G. reaction of benzylmagnesium chloride with 2-cyclohexenone (in presence of cuprous chloride)     

Total synthesis of resolvin E1

Resolvin E1 (RvE1), which is an endogenous mediator to resolve inflammation, was synthesized by Wittig reaction between the C15-C20 aldehyde and the C10-C14 phosphonium salt possessing the vinyl iodo moiety followed by Suzuki-Miyaura coupling of the resulting vinyl iodide with the vinyl borane of the C1-C9 part, which was derived from the corresponding acetylene by hydroboration. The C5 and C18 chiral centers in these parts were created by the kinetic resolution of the racemic γ-TMS allylic alcohols using the asymmetric epoxidation, while that of the C10-C14 part was constructed by the asymmetric hydrogen transfer reaction of the corresponding γ-TMS acetylene ketone.     

Enantioselective syntheses of monotetrahydrofuran Annonaceous acetogenins tonkinecin and annonacin starting from carbohydrates.

The total synthesis of two mono-THF acetogenins, tonkinecin (1) and annonacin (2), is reported in full detail. Terminal acetylene 3 prepared from D-glucono-delta-lactone and asymmetric dihydroxylation was employed as a common intermediate for both targets 1 and 2. Pd(0)-catalyzed coupling reaction of 3 with vinyl iodides 4 and 5, the chiral centers of which were taken from D-xylose and S-(-)-ethyl lactate, afforded enyne 26 and 27, respectively. Selective hydrogenation of 26 or 27 with diimide followed by removal of MOM ethers completed the synthesis of 1. A coupling reaction between the lithium derivative of 3 and epoxide 6 in the presence of boron trifluoride etherate gave 42. Both chiral centers in epoxide 6 were taken from L-ascorbic acid. Subsequent catalytic hydrogenation and MOM protection led to 43b. Introduction of the butenolide moiety by aldol condensation of protected S-lactal followed by cleavage of all MOM ethers completed the synthesis of 2.     

辣椒素和辣椒酯的合成

对以己内酯为起始原料合成辣椒素的工艺进行全新改进, 直接以6-溴己酸乙酯为起始原料, 经6步反应合成了目标化合物辣椒素及其同系物辣椒酯.     

Total synthesis and NMR investigations of cylindramide

Cylindramide (1) was built up from three components: a hydroxyornithine derivative 7, a tetrazolylsulfone 8, and a substituted pentalene subunit 9. Derivative 7 was prepared in a six-step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N-Boc-3-aminopropanal (12). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22. The synthesis of the pentalene fragment 9 started from cycloocta-1,5-diene 26, that was converted into enantiopure bicyclo[3.3.0]octanedione 29. The latter was functionalized to give derivative 9. The total synthesis was accomplished by inducing C-C bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia-Kocienski conditions, macrocyclization, and subsequent Lacey-Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1H and 13C NMR spectroscopic investigations (DQF-COSY, ROESY spectra), the stereochemistry of synthetic cylindramide (1) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest-energy structures for cylindramide.     

Synthesis of chondramide A analogues with modified β-tyrosine and their biological evaluation

Starting from cinnamates 9 , obtained by Wittig reaction or Heck coupling, the diols 17 were prepared by asymmetric dihydroxylation. This was followed by a regioselective substitution of the 3‐OH group with hydrazoic acid under Mitsunobu conditions. Methylation of the 2‐OH group and reduction of the azide group led to the β‐tyrosine derivatives 8 . Condensation with the dipeptide acid 6 furnished the tripeptide part of the chondramides. The derived acids 21 were combined with the hydroxy ester 7 to the esters 22 . Cleavage of the tert‐butyl groups and intramolecular lactam formation gave rise to the chondramide A analogues 2 b – k . Growth inhibition assays showed most of the analogues to be biologically active. Some of them even reach the activity of jasplakinolide. It can be concluded that the 4‐position of the aryl ring in the β‐tyrosine of chondramide A tolerates structural modifications quite well.     

Synthesis of phytyl- and chroman-derivatized photoaffinity labels based on alpha-tocopherol

Photoaffinity analogues of alpha-tocopherol have been prepared by substituting photosensitive functional groups at either the terminus of an alkyl chain of varying length mimicking the phytyl tail or on C-3 of the chroman portion of tocopherol. The alkyl chain-modified compounds 2a-d contain a hexyl to nonyl alkyl chain extending from C-2 of the chroman, terminating in a tetrafluoroazidobenzyloxy group. These compounds were prepared starting from the commercially available Trolox acid 4, followed by esterification, protection, and reduction to the silyl-protected Trolox aldehyde 7, which was coupled using Wittig chemistry to different omega-hydroxyphosphonium bromides. Reduction of the alkene product, coupling with p-azidotetrafluorobenzyl bromide, and deprotection of the phenolic silyl group gave compounds 2a-d in excellent yields. Chroman-functionalized photoaffinity labels were synthesized starting from the protected tocopherol chromene 16b which was a key intermediate for preparation of a 3-hydroxy derivative, either by reduction of epoxides produced directly with Jacobsen's catalysts or by treatment with NBS in wet DME to give two stereoisomeric bromohydrins which were cyclized and reduced to give the phenol-protected C-3 alcohols 19a,b. These alcohols were then converted to diazoacetate esters, and the protecting group was removed to give 3-diazoacetoxy alpha-tocopherols 3a,b.     

Synthesis of site-specifically labeled arachidonic acids as mechanistic probes for prostaglandin H synthase

[structure: see text] Prostaglandin H synthase catalyzes the first committed step in the biosynthesis of prostaglandins and thromboxane. Herein we report the synthesis of four site-specifically labeled arachidonic acids for investigation of the radical intermediate formed during this enzymatic reaction. Two compounds were prepared using a common C9-C11 fragment, while another target was synthesized using a previously reported advanced intermediate. An alkyne coupling followed by hydrogenation and Wittig reaction was used to prepare the final labeled substrate.     

Preparation of (RS)-5-Amino-3-carboxypentanoic Acid (1)

(RS)-5-Amino-3-carboxypentanoic acid (1) was prepared by a Wittig reaction of N-benzoylglycinal (3) with the phosphorane (4), followed by catalytic hydrogenation and acid hydrolysis.     

保幼激素类似物11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯的简便全合成

从价廉的丙酮出发,首先经羟醛缩合、脱水、氧化、酯化、溴代反应合成了4-溴-3-甲基-2-丁烯酸异丙酯,继而与亚磷酸三乙酯反应得到了Wittig-Homer试剂,随后与香茅醛发生Wittig-Horner反应,最后在阳离子树脂催化作用下与甲醇醚化,成功地全合成了具有保幼激素活性的昆虫生长调节剂11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯.所得标题化合物的四种异构体中,具有较高生物活性的(2E,4E)-异构体的含量达66%.各步所合成化合物的结构经1H NMR,IR,MS分析确证.     

Highly efficient synthesis of linear pyrrole oligomers by twofold Heck reactions

The twofold Heck reaction of the vinylpyrroles 3a and 3b with the iodobenzenes 4a-c led to the linear pyrrole oligomers 5, 6, and 7. The synthesis of both symmetrical and unsymmetrical oligomers, such as 10a and 10b, was also accomplished by a Heck reaction of 8 and 9 and by a Heck reaction of 3a and 11 followed by a Wittig reaction and a second Heck reaction with 8. The pentacyclic oligomers 14 and 19 were prepared by a twofold Heck reaction of 13 with 4 and by a twofold Heck reaction of 15 with 16 followed by a Wittig reaction and a twofold Heck reaction with 8.     

Total synthesis of the antiinflammatory and proresolving protectin D1

Stereoselective total synthesis of protectin D1 was completed through construction of the Z,E,E-triene structure by using the Suzuki coupling between the vinyl borane (C13-C22) and the vinyl iodide (C1-C12). The Z-enyne, the acetylene precursor of the vinyl borane was synthesized from optically active γ-TMS allylic alcohol in a straightforward way. On the other hand, the vinyl iodide was prepared by using Wittig reaction between the C8-C12 aldehyde possessing the requisite iodo-olefin moiety and the C1-C7 phosphonium iodide.     

Rasta Resin–PPh3–NBniPr2 and its Use in One‐Pot Wittig Reaction Cascades

A new triarylphosphine–tertiary amine bifunctional polymeric reagent has been prepared and used effectively in a variety of one‐pot Wittig reactions. The design of this reagent resolved a deficiency of a previously reported related material, and allowed it to perform more efficiently in such reactions. Furthermore, it was readily recyclable, and was also successfully applied in cascade processes involving one‐pot Wittig reactions followed by either a conjugate reduction or a reductive aldol reaction. In these reaction cascades, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for the subsequent reaction.     

Chemoenzymatic Synthesis of Pleiogenone A: An Antiproliferative Trihydroxyalkylcyclohexenone Isolated from Pleiogynium timorense

The first total synthesis of polyhydroxylated cyclohexenone 1 , isolated from Pleiogynium timorense and named pleiogenone A, is reported that also serves as a proof of structure and absolute configuration. Enzymatic dihydroxylation of benzoic acid with R. eutrophus B9 provided enantiomerically pure diene diol 6 . Elaboration of the carboxylate moiety to the alkyl side chain was followed by singlet oxygen cycloaddition to furnish an endoperoxide whose reduction with thiourea led to cyclitol 19 . Several protective operations were required before oxidation and the final extension of the side chain by a Wittig reaction. After final deprotection of the acetonide functionality the desired pleiogenone A ( 1 ) was obtained in 14 operations from benzoic acid.     

Total synthesis of (-)-callystatin A

[reaction: see text] The enantioselective synthesis of callystatin A is described. The pivotal step in the synthesis is the stereoselective aldol reaction that generates the beta-hydroxy ketone moiety. Utilizing the allylic strain within the ethyl ketone precursor, we were able to generate the all-syn configuration of callystatin A. For the construction of the two diene moieties, both a Heck coupling and a Wittig reaction were employed.     

Synthesis of four n-alkanes with terminal dipolar substituents

12-Nitrododecanol, 1,12-dinitrododecane, 1,24-dinitrotetracontane and 2,15-diaminohexadecan-1,16-dioioc acid were prepared from the common intermediate 12-bromododecanol. This bromoalcohol, being prepared from cyclododecanone, is free of homologous bifunctional impurities. The functionalised 24 carbon chain was prepared by a Wittig reaction of 12-bromododecanal with the triphenylphosphonium salt of 12-bromododecanal ethylene acetal using ‘naked’ carbonate anion to provide the base. The resulting bromoacetal was converted to 24-bromotetracont-12-enol, both this and the 12-bromododecanol were converted to the corresponding α,ω-di-iodides and then to the desired α,ω-dinitro compounds. The α-amino acid functionality can be introduced on an α,ω-dihalide with the anion of either diethyl 2-acetylaminopropan-1,3-dioate or benzylidene glycine ethyl ester. Also detailed is the previously unreported reduction of a carboxylic acid to an alcohol by borane-dimethyl sulphide in dichloromethane.     

First preparation of (+)-spathulenol. Regio- and stereoselective oxidation of (+)-aromadendrene with ozone.

(+)-Spathulenol was prepared for the first time in three reaction steps from (+)-aromadendrene by two subsequent ozonizations the second of which was regio- and stereoselective, followed by a Wittig reaction. The overall recycle yield was 13%.     

Syntheses of polyfunctionalized resveratrol derivatives using Wittig and Heck protocols

Improved protocols for Wittig reaction and palladium-catalyzed Heck coupling give expedient access to a series of unprecedented polyfunctionalized artificial-resveratrol derivatives. In the modified Wittig protocol, trimethylsilyl was used as a highly valuable protective group of the phenolic functions of starting aromatic materials. A clean O-alkylation of hydroxylated stilbenes with ethylene carbonate was also conducted. Thus, Wittig reaction followed by hydroxyethylation take place one-pot with only carbon dioxide as waste. Additionally, a palladium-catalyzed Heck coupling strategy was developed by using ferrocenyl phosphane ligands, and multi-functionalized hydroxylated stilbenes were obtained without the need of any protection/deprotection sequence. Up to six functional groups are introduced by these procedures, which limit the number of reactions steps, the waste toxicity, and the use of costly reagents.