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Industrial-scale synthesis of eldecalcitol is described. AA highly diastereoselective epoxidation of p-methoxybenzyl (PMB) protected dienol at room temperature provides the key epoxide intermediate...

Total synthesis of marine secondary metabolite nafuredin B has been achieved for the first time using a convergent strategy. Sharpless epoxidation followed by acid catalyzed epoxide opening were adopted to install the tetrasubstituted hydroxy center, whereas the iterative Julia-Kocienski olefination, Wittig olefination and HWE olefination afforded the olefin bonds. Ring closing metathesis in the presence of a free tetrasubstituted hydroxy group provided the unsaturated δ-lactone moiety. This synthetic study provided unambiguous structural confirmation of the isolated nafuredin B.

The M06-2X DFT functional has been employed to examine monomeric titanium(IV) hydroperoxo catalysts that model the individual steps in the dimeric titanium(IV)-catalyzed Sharpless reaction. This is the first example of a transition structure for titanium(IV) tert-butyl hydroperoxide-catalyzed epoxidation that describes the molecular motion required for oxygen atom transfer. These epoxidation catalysts have been examined for both bimolecular reactions with E-2-butene and the intramolecular epoxidation of allyl alcohol. The transition structure for the bimolecular peroxyacetic acid epoxidation of E-2-butene has been shown to be spiro in nature, and likewise, the intramolecular epoxidation of allyl alcohol is also nearly spiro. The significance of the O-C-C═C dihedral angle of allyl alcohol is examined for the Ti(IV) tert-butyl hydroperoxide epoxidation mechanism. Evidence is presented that supports a hexacoordinate titanium peroxo environment that exists in the dimeric form of the Sharpless catalyst. The mechanism for a 1,3-rearrangement of the alkoxide ligand in a titanium hydroperoxide to the Ti center in concert with oxygen atom transfer of the proximal oxygen to the C═C bond of the substrate is presented. The dimerization of Ti(IV)-(R,R)-diethyl tartrate-diisopropoxide and its hydrolysis have been calculated. The mechanism for rapid ligand exchange with alkyl hydroperoxides involving the Ti(O-i-Pr)4 precursor is examined to show how the active epoxidation catalyst is produced.

Synthesis of the C1–C13 fragment of eribulin mesylate has been accomplished. It features a highly stereoselective construction of a trans-dihydropyran framework using three key reactions: (1) Sharpless epoxidation, (2) regioselective ring opening, and (3) olefin metathesis.

We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita–Baylis–Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation.

The Katsuki-Sharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. The complete understanding of this reaction mechanism depends on the identification and description of species formed from Ti(IV) alkoxides and alkyl tartrates precatalysts. Despite previous reports on the nature of a bimetallic catalyst based on IR spectroscopy and NMR analysis, some debate remains. Therefore, we carried out mass spectrometry analysis by direct extraction of the ions from the reaction media by ESI(-)-FT-ICR and evaluated the observed ions by CID and IRMPD experiments. These techniques allowed us to detect carboxylates that correlate to the species in the reaction media and to confirm the actual presence of the titanium-tartrate complexes in solution. Our IRMPD results suggest the carboxylate dimer as an asymmetric species with two tartrates coordinated to a single Ti atom, while the other Ti center is coordinated by labile alkoxydes that could be easily exchanged by the organic peroxide and the substrate, allowing the epoxidation reaction to take place.

In this work, we investigated the catalytic effects of a Sharpless dimeric titanium (IV)–tartrate–diester catalyst on the epoxidation of allylalcohol with methyl–hydroperoxide considering four different orientations of the reacting species coordinated at the titanium atom (reactions R1–R4) as well as a model for the non-catalyzed reaction (reaction R0). As major analysis tools, we applied the URVA (Unified Reaction Valley Approach) and LMA (Local Mode Analysis), both being based on vibrational spectroscopy and complemented by a QTAIM analysis of the electron density calculated at the DFT level of theory. The energetics of each reaction were recalculated at the DLPNO-CCSD(T) level of theory. The URVA curvature profiles identified the important chemical events of all five reactions as peroxide OO bond cleavage taking place before the TS (i.e., accounting for the energy barrier) and epoxide CO bond formation together with rehybridization of the carbon atoms of the targeted CC double bond after the TS. The energy decomposition into reaction phase contribution phases showed that the major effect of the catalyst is the weakening of the OO bond to be broken and replacement of OH bond breakage in the non-catalyzed reaction by an energetically more favorable TiO bond breakage. LMA performed at all stationary points rounded up the investigation (i) quantifying OO bond weakening of the oxidizing peroxide upon coordination at the metal atom, (ii) showing that a more synchronous formation of the new CO epoxide bonds correlates with smaller bond strength differences between these bonds, and (iii) elucidating the different roles of the three TiO bonds formed between catalyst and reactants and their interplay as orchestrated by the Sharpless catalyst. We hope that this article will inspire the computational community to use URVA complemented with LMA in the future as an efficient mechanistic tool for the optimization and fine-tuning of current Sharpless catalysts and for the design new of catalysts for epoxidation reactions.

An enantiomerically pure substance has paramount physiological importance. Synthetic chemists aimed to produce drug molecules primarily target to synthesize pure enantiomer. Enantiomers are optically active stereoisomers so in order to accomplish products with high enantiomeric excess, asymmetric synthesis must be designed judiciously. Mimicking nature’s selective aptitude of biosynthesis is always considered a crucial challenge for synthetic chemists. The main target of drug designing is to attain skill in this specialized section. Racemization during asymmetric synthesis occasionally disappoints synthetic chemists by widely disrupting biophysical, biochemical characteristics of the synthesized compound. Kinetic resolution, however, is able to separate two enantiomers. Among innumerable synthesis, only a few are found to be associated with high enantiomeric excess yield. Contribution of enantioselective epoxide synthesis by Sharpless epoxidation is no less important in drug industry. Most striking feature of Sharpless epoxidation is materials used for producing enantiospecific epoxide are inexpensive. Product spread consisting of one predominating chiral epoxide is efficiently resolved. The current communication is aimed to analyse Sharpless epoxidation from analytical angle of a chemist using a model study of transition state structure using DIPT as chiral auxiliary and drives to find the underlying basis responsible for channelizing only one enantiomer at the suppression of other.

The unified reaction valley approach (URVA) differs from mainstream mechanistic studies, as it describes a chemical reaction via the reaction path and the surrounding reaction valley on the potential energy surface from the van der Waals region to the transition state and far out into the exit channel, where the products are located. The key feature of URVA is the focus on the curving of the reaction path. Moving along the reaction path, any electronic structure change of the reacting molecules is registered by a change in their normal vibrational modes and their coupling with the path, which recovers the curvature of the reaction path. This leads to a unique curvature profile for each chemical reaction with curvature minima reflecting minimal change and curvature maxima, the location of important chemical events such as bond breaking/forming, charge polarization and transfer, rehybridization, etc. A unique decomposition of the path curvature into internal coordinate components provides comprehensive insights into the origins of the chemical changes taking place. After presenting the theoretical background of URVA, we discuss its application to four diverse catalytic processes: (i) the Rh catalyzed methanol carbonylation&mdash, the Monsanto process, (ii) the Sharpless epoxidation of allylic alcohols&mdash, transition to heterogenous catalysis, (iii) Au(I) assisted [3,3]-sigmatropic rearrangement of allyl acetate, and (iv) the Bacillus subtilis chorismate mutase catalyzed Claisen rearrangement&mdash, and show how URVA leads to a new protocol for fine-tuning of existing catalysts and the design of new efficient and eco-friendly catalysts. At the end of this article the pURVA software is introduced. The overall goal of this article is to introduce to the chemical community a new protocol for fine-tuning existing catalytic reactions while aiding in the design of modern and environmentally friendly catalysts.

The synthesis of enantiomerically pure B-ring fluorinated catechin derivatives is presented. In a convergent approach the chromane was obtained by reaction of a lithiated fluoro-resorcine with an optically active epoxide. The latter was prepared from 3,4-difluorobenzaldehyde by reaction with vinylmagnesium bromide followed by Sharpless epoxidation. The protocol provides access to both fluorinated catechin as well as epicatechin derivatives.

A study aimed at the synthesis and structure optimization of new, efficient, optically active β-amino alcohol ligands with a structure suitable for immobilization on magnetite nanoparticles has been carried out. The optimized homogeneous amino alcohol catalysts 13a and 13b, the chirality of which arises from the Sharpless epoxidation of suitable allyl alcohols, were tested by employing the well-established enantioselective amino alcohol-promoted addition of diethylzinc to benzaldehyde, giving the corresponding benzyl alcohol with nearly quantitative yield and ee = 95%. Then, their broad applicability as chiral catalysts was evaluated by carrying out the same reaction on a family of aldehydes, including variously substituted aromatic ones as well as an aliphatic analogue. The results have confirmed the validity of the fine-tuning process performed on ligands 13a and 13b. In fact, both exhibited excellent catalytic activity as demonstrated by the chemical yields and ee obtained from all the tested aldehydes, almost independent of the position and type of substitution in the aromatic ring.

Described herein are the first total syntheses of naturally occurring antitumor agents disorazoles A1 and B1 and the full structural assignment of the latter. The syntheses were achieved through convergent strategies employing enantioselective constructions of the required building blocks, including a novel Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing substrates that led selectively to both enantiomeric forms of an epoxy vinyl stannane, and a series of coupling reactions, including a Wittig reaction, a Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi macrolactonization.

A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn -stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti -stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis -2-butene-1,4-diol respectively.

A stereoselective synthesis of entecavir, an anti-hepatitis B (HBV) drug, was accomplished by a regioselective isopropylidene cleavage, stereoselective Sharpless epoxidation, and TiIII-mediated regio- and stereoselective epoxide cleavage as key steps.

The first total syntheses of 9-epoxyfalcarindiol 1a and its diastereomer 1b have been achieved. Central to our approach were the Zn-cyclopropane-based amino alcohol catalyzed enantioselective alkynylation of acrolein, the diastereoselective addition of a diynic ester to an epoxy aldehyde, and the asymmetric Sharpless epoxidation of allylic alcohol catalyzed with L-(+)-diethyl tartrate and Ti(OiPr)4.

A highly diastereoselective and efficient convergent synthesis of mupirocin H starting from (+)-(R)-Roche ester was achieved. Grubbs cross metathesis was employed as the key step in the pathway to generate an important E-olefin intermediate. Other processes utilized in the route include a Pd-catalysed stereoselective substitution reaction of a cis epoxide, Sharpless epoxidation followed by Red-Al promoted epoxide ring opening, and Seebach methylation and a TEMPO/BAIB mediated oxidation-lactonization sequence. Finally, we observed that mupirocin H inhibits SbnE, a synthetase required for staphyloferrin B biosynthesis.

In order to better understand the epoxide-formation step of the Sharpless epoxidation process, a set of 263 oxygen-transfer reactions reflecting the complexity of the Sharpless epoxidation process were studied using density functional theory (DFT) and Bader's quantum theory of atoms in molecules (QTAIM). The diversity within these reactions reflects the different ligands in the coordination sphere of vanadium and also different substrates (alkene and an allylic alcohol both free and in the form of an alcoxo ligand). The transition states for 76 of these reactions were also characterized using DFT and QTAIM, allowing for an estimation of the impact of the different ligands and substrates on the activation barriers. A smaller subset of the latter was further subjected to an ab initio molecular dynamics (AIMD) simulation coupled to QTAIM analysis. The results show that the type of active catalyst plays an important role in the thermodinamic outcome of these reactions, with vanadium(V) tert-butylhydroperoxide adducts being responsible for the most exoenergetic reactions. On the other hand, the different ligands tested play only a limited role in modulating the thermodynamics and kinetics of these reactions. Moreover, no evidence was found to support a thermodynamic or kinetic preference for the epoxidation of an allylic alcohol over that of an unfunctionalized alkene. However, the results suggest that the reaction path is strongly influenced by the orientation of the substrate upon approximation to the active catalyst, confirming the well-known regioselectivity of the Sharpless epoxidation process.

A stereoselective synthetic approach to the natural product (+)-nivetetracyclate A is reported. The tetracyclic skeleton was assembled in a convergent manner by an alkylation to a diarylmethane and subsequent Friedel-Crafts acylation. Further key steps are an asymmetric Sharpless epoxidation and the boron trifluoride-mediated diastereoselective rearrangement of an epoxy alcohol to a β-hydroxy aldehyde. Optimized timing for the deprotection step and the chemo- and stereoselective Noyori -transfer hydrogenation of a 1,4-diketone allowed the late stage introduction of the C4 stereocenter.

A facile and concise synthesis of β-carboline alkaloids, such as (–)-isocyclocapitelline and (+)-cyclocapitelline, has been achieved from commercially available geraniol through a unified strategy. The key steps involved in this synthesis are Sharpless epoxidation, intramolecular ring opening of epoxide, Pictet-Spengler reaction, and dehydrogenative aromatization using 10% palladium/carbon in xylene under neutral conditions.

Nannocystin A, a structurally unique 21-membered macrocyclic depsipeptide with low nanomolar inhibitory activity against elongation factor 1A, was synthesized according to a strategy involving the vinylogous Mukaiyama aldol reaction, Sharpless epoxidation, olefin metathesis, the Mitsunobu reaction, and a palladium-catalyzed intramolecular Suzuki coupling of a highly complex cyclization substrate. The overall synthesis is efficient and paves the way for preparation of analogues for drug development efforts.

When investigating the Sharpless epoxidation of enol-protected 4-hydroxy-1,2-cyclopentanediones, the ability of the asymmetric Ti(O i Pr) 4 /tartaric ester complex to discriminate between enantiomeric epoxides formed in situ was discovered, leading to the epoxide opening reaction of only one enantiomer. This observation was used in the kinetic resolution of racemic substituted 2,3-epoxy-4-hydroxy-cyclopentanol, to afford enantiomerically enriched epoxyalcohols in good yields and with ees up to 96%.

Amphidinolide N, the structure of which has been recently revised, is a 26-membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-(N-benzyloxycarbonyl-N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol.

A facile and stereoselective synthesis of C1–C9 and C9–C17 fragments of (+)-13-deoxytedanolide and studies towards the synthesis of (+)-13-deoxytedanolide was accomplished in 20 linear steps. The key transformations of fragment 6 are Sharpless asymmetric dihydroxylation and preparation of terminal olefin from primary alcohol utilising organo selenium reaction. The key transformations of fragment 7 are from Sharpless epoxidation and Crimmin’s syn aldol chemistry.

The relative and absolute configurations of xiamenmycin A, a benzopyran compound isolated from Streptomyces xiamenensis 318 with a highly potent anti-fibrotic activity, have been characterized through the total synthesis. The key steps include the construction of the 3-chromanol moiety via Sharpless epoxidation followed by regio- and diastereo-selective cyclization and introduction of the threonine moiety at a later stage via Pd-catalysed aminocarbonylation in a one-pot procedure. The stereochemical assignment of natural xiamenmycin A has been accordingly revised to be 2R, 3S, 3'S, 4'R.

Total synthesis of herboxidiene/GEX1A/TAN-1609 has been accomplished in the 22 longest linear sequences starting from 2-butyne-1,4-diol following our recently developed gold-catalyzed Hosomi-Sakurai type of reaction on lactols with allyltrimethyl silane and Stille cross coupling to assemble the advanced fragment. The synthesis of the C10-C19 fragment was accomplished by means of Sharpless epoxidation and asymmetric alkylation reactions starting from (R)-methyl lactate.

An efficient total synthesis of natural panaxydol 1a and its seven stereoisomers 1b – h was accomplished; four diastereomers of the natural form were prepared for the first time. Our strategy involves the Cadiot-Chodkiewicz cross-coupling reaction of chiral terminal alkynes with bromoalkynes, the asymmetric alkynylation of aldehydes, and the enantioselective Sharpless epoxidation of allylic alcohols. Preliminary in vitro cytotoxicity evaluation indicated that some synthetic panaxydols possess anticancer activities, and (3 S ,9 R ,10 S )-panaxydol 1e showed a particularly promising cytotoxic effect.

Using a one-pot Sharpless asymmetric epoxidation/regioselective epoxide ring-opening as a key step, the protecting-group-free total synthesis of goniothalesdiol A was accomplished in only three steps starting from commercially available trans -cinnamaldehyde in 55.1% overall yield. In 6 previously reported total syntheses, 6–11 steps were required.

The stereoselective synthesis of resolvin D4 (RvD4) was achieved using the Wittig reaction of the C1–C10 dienal with the known C11–C22 phosphonium salt. The (S,E)-enantiomer (S)-10, corresponding to the C1–C8 part, was synthesized in 95% ee by the asymmetric transfer hydrogenation reaction of the corresponding acetylenic ketone followed by Red-Al reduction. Sharpless epoxidation of this alcohol using Ti(O-i-Pr)4/l-(+)-DIPT as a catalyst produced anti epoxy alcohol with >99% ee as the sole product in 82% yield. A subsequent functional group manipulation, including removal of the PMB group, produced the alcohol, which upon Swern oxidation afforded anti 4-hydroxy-5-TBS-oxy enal via epoxide ring opening of the resulting aldehyde. The Horner–Wadsworth–Emmons reaction was used to add the C9–C10 enal part to this aldehyde, and the resulting dienal was subjected to the Wittig reaction with C11–C22 phosphonium salt to furnish the entire structure of RvD4. Conversion of the primary alcohol to the methyl ester and d...

The stereospecific total synthesis of the pro-resolving and tissue-regenerative Protectin sulfido-conjugates: 16R,17S-PCTR1, 16R,17S-PCTR2, and 16R,17S-PCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 16S,17S-epoxy-Protectin methyl ester was synthesized using the Sharpless catalytic asymmetric epoxidation to generate the chiral centers at C16 and C17. A Cs2CO3 promoted coupling provided the skipped diyne intermediate. Wittig reactions and epoxide opening with glutathione, l -cysteinylglycine, and l -cysteine methyl ester hydrochloride, respectively, were the key steps in the synthesis.

The total synthesis of the nonenolide xyolide is described as a convergent synthesis in 16 steps from the commercially available starting material butane-1,4-diol. The key reactions involved are: Sharpless­ asymmetric epoxidation, Pinnick oxidation, acid-mediated nucleophilic regioselective epoxide ring opening, Steglich esterification, and ring-closing metathesis.

Herein, we report the total synthesis of proposed structure of polyporolide 1 via Barbier allylation, Sharpless epoxidation, Titanium(IV) promoted regioselective ring-opening reaction of epoxy homoallyl alcohol and acid catalyzed intramolecular lactonization as the key steps. Also a chiron approach was adopted for the same in greater overall yields.

A novel autophagy inducer, (+)-epogymnolactam (1), was first synthesized from cis-4-benzyloxy-2-butene-1-ol (2) in eight steps. A reliable preparation of optically pure epoxy alcohol (+)-3 from monobenzyl derivative (2) was established by a tandem strategy, Sharpless epoxidation/lipase kinetic resolution.

The first total synthesis of a naturally occurring styryllactone secondary metabolite parvistone B has been achieved in five steps with an overall yield of 67 % from readily available trans-cinnamaldehyde. It exhibits cytotoxicity against different human tumour cell lines. Key features of our synthetic strategy include Maruoka asymmetric allylation, Sharpless epoxidation, ring-closing metathesis, and regioselective epoxide ring-opening. This synthetic strategy constitutes a step economical, atom economical and protecting group-free total synthesis.

Nannocystin A is a novel 21-membered macrolactone isolated from myxobacterium Nanocystis sp. It is a potent elongation factor 1 inhibitor and inhibits cancer cell line growth at nanomolar concentrations. In this work, a concise asymmetric total synthesis of nannocystin A has been developed, which features Sharpless epoxidation, Stille coupling, and final macrolactamization.

An efficient total synthesis of macrosphelide I, has been achieved starting from commercially available chiral materials, ethyl (S)-lactate and methyl (R)-3-hydroxybutyrate. Titanium(IV) promoted the regioselective nucleophilic opening reaction of epoxy alcohol with benzoic acid, Sharpless epoxidation, ring-closing metathesis and Yamaguchi esterification as key steps for the construction of the 16-membered macrotriolide.

A stereoselective synthesis of tetrahydropyran–tetrahydrofuran (THP–THF) core 2 of (+)-muconin (1) has been achieved using Prins cyclization as a key step to construct tetrahydropyran moiety. Other important transformations such as Wittig olefination, Sharpless epoxidation, regio-, and stereoselective exo-cyclization of the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy alcohol, Grignard reaction, and Barton–McCombie reaction are successfully employed to accomplish the synthesis of THP–THF core 2.

The first total synthesis of a naturally occurring styryllactone secondary metabolite parvistone B has been achieved in five steps with an overall yield of 67 % from readily available trans-cinnamaldehyde. It exhibits cytotoxicity against different human tumour cell lines. Key features of our synthetic strategy include Maruoka asymmetric allylation, Sharpless epoxidation, ring-closing metathesis, and regioselective epoxide ring-opening. This synthetic strategy constitutes a step economical, atom economical and protecting group-free total synthesis.

Starting from the conveniently available ex-chiral pool building block (R,R)-hexa-1,5-diene-3,4-diol, the ten-membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation.

Epoxy alcohol anti-10, derived from a desymmetrizing Sharpless epoxidation (up to 97 % ee) of divinylcarbinol 9, provided the unsaturated 1,3-diol syn-11 upon treatment with RedAl®; syn-11 was converted into the α,β-unsaturated esters (E)- or (Z)-7b in three steps. Cu-promoted 1,4-addition of vinylmagnesium halides to the (E)-ester proceeded with diastereoselectivities of up to 91 % and Cu-catalyzed 1,4-additions with diastereoselectivities of up to 82 %. The potassium enolate of the major vinylation product syn-22b was hydroxylated by the Davis oxaziridine with perfect but unprecedented diastereoselectivity. The resulting hydroxy ester, α,βsyn,β,γsyn-32, furnished the “eastern moiety” building block 6 of the title compounds in three steps.

A stereocontrolled synthesis of the enantiomerically pure epoxide 7b from propargyl ether 15 has been realized in 15 steps. Epoxide 7b represents a building block for the “eastern” moieties of the title compounds. Key steps in our approach were a desymmetrizing Sharpless epoxidation ( anti,cis-16), the selective processing of the bis-enolate of the bis(tert-butyl alkoxyacetate) 11 through a diastereoselective [2,3]-Wittig rearrangement ( syn,syn-9), and a stereo- and chemoselective iodolactonization ( 35). The CO2H groups of dicarboxylic acid 37 were differentiated in a one-pot bis-oxidation reaction. The latter entailed the novel transformation of HO2CCH2-O-alkyl into AcOCH2-O-alkyl.

The total synthesis of enantiomer of pyrenophorol, non-natural isomer of pyrenophorol, has been accomplished in 12 steps from enantiomerically pure ( R )-Propylene oxide prepared by hydrolytic kinetic resolution. Other key steps are Sharpless epoxidation, reductive elimination of iodoepoxide, and Mitsunobu reaction for the construction of the macrolactone.

The total synthesis of the 2,6-disubstituted piperidine alkaloid (−)-andrachcinidine is reported using Keck’s asymmetric allylation, Sharpless epoxidation, nucleophilic substitution, and intramolecular aza-Michael addition as the key steps.

A concise total synthesis of the cytotoxic marine natural product amphidinolide X (1) is described. A key step of the highly convergent route to this structurally rather unusual macrodiolide derivative consists of a newly developed, highly syn selective formation of allenol 6 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to give dihydrofuran 7 containing the (R)-configured quarternary sp3 chiral center at C19 of the target. The anti-configured chiral centers at C10 and C11 were formed by the palladium-catalyzed, Et2Zn-promoted addition of propargyl mesylate 12 to the functionalized aldehyde 11. The key fragment coupling at the C13−C14 bond was achieved by the “9-MeO-9-BBN” variant of the alkyl-Suzuki reaction. Finally, the 16-membered macrodiolide ring was formed by a Yamaguchi esterification/lactonization strategy.

(+)-Mueggelone (I) is synthesized from commercially available and inexpensive starting materials via Sharpless epoxidation, Jacobsen resolution, lactonization and cross metathesis.

A stereoselective total synthesis of multiplolide A (1) and of its diastereoisomer 2 was described from easily accessible starting materials (Schemes 2–4). The synthetic strategy involves a Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring-closing metathesis (RCM).

The first stereoselective total synthesis of the naturally occurring anti-emetic diarylheptanoid (3R,5R)-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol (1) was accomplished starting from 4-hydroxybenzaldehyde and involving a Sharpless kinetic resolution and an asymmetric epoxidation as the key steps (Scheme 2). The enantiomer 1a of this compound was also simultaneously prepared.

The enantioselective synthesis of natural brevipolide H is reported for the first time. By way of Sharpless epoxidation of penta-1,4-dien-3-ol, both enantiomerically pure epoxides were converted to the corresponding olefins for cross metathesis. Subsequent transformations, including epoxide ring opening, esterifications, cyclopropanation, oxidation and ring-closing metathesis, provided the target molecule. This synthesis successfully addresses previous shortcomings in preparing brevipolides.