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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.

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.

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.

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.

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.

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.

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.

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.

Aspicilin (1), an eighteen membered macrolide with four stereocenters, was synthesized using (3R,4R)-1,5-hexadiene-3,4-diol and (S)-propylene oxide as the starting materials. Sharpless epoxidation on the protected dienediol generated the required three consecutive stereocenters, and malonic ester synthesis added the acetyl unit. Yamaguchi protocol was applied to form the key ester with two terminal olefins ready for the ring-closing metathesis. RCM, hydrogenation, selenylation, oxidation and deprotections gave aspicilin with 4.7% total yield.

National Basic Research Program (973 Program) of China [2010CB833200]; National Natural Science Foundation of China [20832005]; Natural Science Foundation of Fujian Province of China [2011J01054]

An efficient enantioselective synthesis of deoxymannojirimicin is reported. It is based on the unusual Sharpless asymmetric epoxidation of a silyl-substituted allylic 1,4-amino alcohol coupled with a further highly stereoselective intramolecular aldolization. Both enantiomers of deoxymannojirimicin are available. An orthogonally protected polyhydroxylated piperidine was prepared, which could formally lead to other members of this piperidine family.

A highly stereoselective first total synthesis of amphidinin B is described. The key steps involved in this synthesis are the generation of the exo-double bond in the C 1 ―C 9 segment, the Barbier allylation, enzymatic kinetic resolution, and the construction of the C 10 ―C 21 segment by Sharpless asymmetric epoxidation, base-induced epoxide ring-opening, radical cyclization, diastereoselective reduction of the exo-cyclic double bond, one-pot allylation followed by debenzylation, Evans alkylation, and Yamaguchi esterification.

Optical antipodes of 4-alkyl-γ-lactones 3 have been prepared by photochemical rearrangement of optically active α,β-epoxy diazomethyl ketones 1 in ethanol to give 4-hydroxy-alkenoates 2, followed by reduction of the alkene bond and subsequent lactonization. The required epoxy diazomethyl ketones 1 were obtained via the following sequence of reactions: alkylation of 2-propyn-l-ol, subsequent reduction to the alkenols 6, Sharpless epoxidation to 2,3-epoxy alcohols 7, oxidation to glycidic esters 8 and finally conversion to diazo ketones 1. The enantiomeric purities range from 84 to 100%.

Optically active oxirane-2-carboxylic esters, prepared from allylic alcohols employing the Sharpless epoxidation, were treated with sodium azide. The azido alcohols obtained were subsequently converted into aziridine-2-carboxylic esters by reaction with triphenylphosphine, in good yields and with high optical purity. Various racemic oxirane-2-carboxylic esters were subjected to the same sequence of reactions.

The regioisomeric epoxy-4-pentenols B and D, readily accessible from 1,4-pentadiene-3-ol A in high stereoisomer purity by Sharpless epoxidation, have been shown to produce various regio- and stereoisomers of amino-4-pentenediols in a controlled manner. The N-protected derivatives of 1- and 3-aminopentenediols 2 and 11, respectively, are suitable for oxidative degradation to amino acid derivatives. Subsequent hydrolysis provides the rare amino-dihydroxy-butyric acid hydrochlorides 9 and 15.

Optically active 2,3-epoxyhexanol obtained from Sharpless asymmetric epoxidation (AE) was regioselectively reduced to 1,3-hexandiol or 1,2-hexandiol. 1,3-Hexandiol was converted to 3-mesyloxyhexyl acetate. The following reaction with CH 3 SK gave 3-methylthiohexanol, which was oxidized through Swern oxidation to produce 3-methylthiohexanal. 5- and 6-Butyl-1,4-dioxan-2-one were formed concurrently by the reaction of 1,2-hexandiol with 2-bromoacetic chloride and the ratio of 5-butyl isomer to 6-butyl isomer was about 1:4. The enantiomeric excess values of both enantiomers of 3-methylthiohexanal and 5(6)-butyl-1,4-dioxan-2-one were about 90%, which were very close to those of 2,3-epoxyhexanol (about 94% ee). No obvious racemization occurred during the transformation from the Sharpless AE products to the final products.

A novel synthetic route has been reported for the synthesis of nonenolide. The syntheses of fragments were initiated from commercially available and inexpensive starting materials. The synthesis involves key steps like Sharpless epoxidation, Jacobsen's resolution, lactonization, and cross-metathesis.

An efficient formal total synthesis of the marine natural product palmerolide A is reported herein, involving 24 longest linear steps. The key features of our synthesis involve a combination of Sharpless epoxidation and Shimizu reaction to construct the syn aldol moiety, a Julia–Kocienski reaction to construct the diene, and ring-closing metathesis to form the macrocycle.

The stereoselective synthesis of (–)-(5R,6S)-erythro-6-acetoxy-5-hexadecanolide, the major component of a mosquito oviposition attractant pheromone, and its enantiomer are reported. The synthesis was completed over seven steps in 28 % overall yield by using Sharpless asymmetric epoxidation and ZrCl4-catalyzed cyclic acetal formation as the key steps. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Trifluoroethanol was converted into difluorinated (racemic) analogues of amicetose and rhodinose by metallated difluoroenol acetal chemistry, protection, release of the latent difluoromethyl ketone, stereoselective reduction and ozonolysis in acidic methanol. A fortuitous separation of diastereoisomers allowed the diastereoisomeric pyranoses to be obtained cleanly. Though reductive defluorination allowed a facile entry to the route, the corresponding monofluoro sugar analogues could not be separated. Instead, Sharpless asymmetric epoxidation followed by epoxide ring-opening with an unusual nucleophilic fluoride source allowed enantiomerically highly enriched and selectively protected fluorodiols to be obtained. Ozonolysis then afforded the methyl pyranosides, which could be transformed in a number of ways.

Enantioselective syntheses of cis-4- and trans-3-hydroxypipecolic acids from 2,3-epoxy-5-hexen-1-ol (7) are described. Regioselective C-3 or C-2 ring opening of the epoxide by the appropriate nitrogen nucleophile is the key step in each route. As enantiomerically enriched epoxy alcohols are readily available in any configuration by Sharpless epoxidation, both enantiomers are equally accessible. This approach was also employed to synthesize the natural product baikiain and the important synthetic intermediate trans-3-hydroxy-2-hydroxymethylpiperidine. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The double asymmetric Katsuki–Sharpless epoxidation of a conjugated diallyl alcohol affords excellent enantioselectivity (>97 % ee), the product being isolated as the stable p-nitrobenzoate 5a or tosylate 5b. The optical purities of the chiral epoxides were determined by HPLC on chiral columns, while the molecular structures of compounds 5a and 7 and the absolute configuration of mono-epoxide 12 were confirmed by X-ray crystallography. Possible π–π stacking interaction has been evaluated by ab initio calculation.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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.

Cryptomoscatone D2 was synthesized stereoselectively from trans-cinnamaldehyde. The synthesis of the triol frame work relied on the creations of the stereocenters independently by utilizing double Maruoka allylations and Sharpless epoxidation. The lactone moiety was constructed by RCM reaction.

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.

δ-Lactone (–)-malyngolide (1) was synthesized by starting from the optically active epoxide 5. Coupling of derivative 3 with propargyl anion 11 and subsequent metal-catalyzed methylation of the triple bond provided 14 incorporating all the carbon atoms of 1. Cyclization to the acetal 16 was achieved via the epoxidation product 15. Adjustment of the oxidation state and removal of protective groups complete the synthesis of 1.

A protecting group free asymmetric total synthesis of (−)-venlafaxine is reported. The strategy employs Sharpless epoxidation and regio-selective epoxide ring opening by an in situ generated Gilman reagent as key steps. This paper reports a 53% overall yield in 6 steps for total synthesis of (−)-venlafaxine.

Wilkinson's catalyst [RhCl(PPh3)3] has been used to conjugate fish oils in high yields under very mild reaction conditions. A catalyst load of 0.35 mol% of RhCl(PPh3)3, 0.43 mol% of (o-CH3C6H4)3P, and 0.87 mol% of SnCl2·2H2O in ethanol solvent at 60°C for 2 d produces 82% conjugated Norway fish oil affords 90% conjugated fish oil in 93% yield. The Sharpless epoxidation procedure has also been employed to epoxidize fish oils. Using 0.34 mol% of CH3ReO3, 8.15 mol% of pyridine, and 1.03 equivalents of aq. 30% hydrogen peroxide in methylene chloride solvent at 25°C for 6 h, the Norway fish oil ethyl ester can be 100% epoxidized in an 86% yield. The Capelin fish oil gives 100% epoxidized fish oil in a 72% yield. Decreasing the amounts of CH3ReO3 and pyridine used in the reaction results in partially epoxidized fish oils.

The synthesis of the pyran core (VI) of macrolactin 3 is based on Sharpless epoxidation, Ti(IV)-promoted nucleophilic regioselective epoxide ring-opening, and oxa-Michael addition as the key steps.

The ability of 19 microorganisms to perform the enantioselective lactonization of racemic γ,δ-epoxy ester 3a and its 7-methyl homolog 3b was checked. It was found that Rhodotorula rubra preferentialy transformed both substrates to (−)-enantiomers of trans δ-hydroxy-γ-lactones with ee 76% for 3a and 24% for 3b. The best efficiency (20–30%) and enantioselectivity (ee 60–100%) of formation of (−)-γ-hydroxy-δ-lactones 6a and 6b was observed for lactonization by Botrytis cinerea and Fusarium semitectum, respectively. Chirality 13:302–307, 2001. © 2001 Wiley-Liss, Inc.

An enantioselective synthesis of cordiachromene is described. An allylic alcohol moiety is first attached in the o-position to the methoxymethoxy substituent in 1-methoxy-4-methoxymethoxybenzene. Then chirality is introduced successively through asymmetric Sharpless epoxidation on the allylic alcohol moiety and regioselective ring-opening. The chiral diol prepared is then cyclized to chromanmethanol with total retention of configuration. Chromenemethanol is obtained after bromination and dehydrobromination. The total synthesis is achieved by reaction between the tosylated chromene chiral moiety and an organomagnesium prenylated compound.

The first stereoselective synthesis of the specific EP 1 receptor agonist, 16,16-dimethyl prostaglandin E 2 1, is described. The key intermediate 3 was obtained from the E-allyl alcohol 6 via Sharpless epoxidation followed by stereospecific transformations to the γ-iodo vinyl compound 3. Two component coupling of 2 and 3, using the dilithiocyanocuprate technology, gave the 1,4-addition product. Mild desilylation and enzymatic ester cleavage produced the optically pure prostaglandin 1 in high yield.

Crystalline (–)-stegobinone [(2S,3R,1′R)]-2,3-dihydro-2,3,5-trimethyl-6-(1′-methyl-2′-oxobutyl)-4H-pyran-4-one (1)], the major component of the female-produced sex pheromone of the drugstore beetle (Stegobium paniceum L.), was synthesized by oxidation of crystalline and the minor component (–)-stegobiol [(2S,3R,1′S,2′S)-2,3-dihydro-2,3,5-trimethyl-6-(2′-hydroxy-1′-methylbutyl)-4H-pyran-4-one (2)] under the appropriate conditions using Jones's chromic acid, Dess-Martin's periodinane or Ley's ruthenium reagent. The latter (2) was synthesized by employing lipase and the Sharpless epoxidation for the introduction of the proper chiral centers. The streostructure of 1 was comfirmed by X-ray analysis.

Although coffee beans have been well studied, the volatile constituents of the coffee flower have not previously been investigated. An extract of coffee flower (Coffea arabica L.) was analyzed by GC–MS and found to contain a significant number of nitrogen-containing aromatic compounds as well as phenylethane derivatives. The novel epoxygeraniols (2,3-epoxygeraniol and 6,7-epoxygeraniol) were also detected as minor components. These epoxides were estimated to be an approximately equal mixture of both enantiomers by chiral GC analysis. Optically active 2,3-epoxygeraniols were synthesized by Sharpless's asymmetric epoxydation (AE), and 6,7-epoxygeraniols were prepared utilizing Sharpless's asymmetric dihydroxylation (AD) as a key step in high optical purities (96–99% ee). Epoxygeraniols were found to possess rosy and muguet-like aromas reminiscent of the living flower. Considerable differences of aroma were perceived between the enantiomers. © 1997 by John Wiley & Sons, Ltd.

Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the effects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. (S)-Iodiconazole was proved to have better antifungal activity than the (R)-isomer. The binding modes of the two isomers with lanosterol 14α-demethylase were clarified by molecular docking.

Sharpless epoxidation of (E)-1-(trimethylsilyl)[1-2H1]oct-1-en-3-o1 (3a) yielded (1S,2S,3S)- and (1R,2R,3R)-1-(trimethylsilyl)-1,2-epoxy[1-2H1]octan-3-ols (4a and 4b, resp.) which were converted in three steps into (S)- and (R)-fluoro[ 2H1]acetic acid (7a and 7b, resp.) in good yields. Their high isotopic and optical purity was established by 1H- and 19F-NMR, mass, and circular-dichroism spectroscopy.

The analytical and preparative scale optical resolution of 1-cyclohexyl-1- phenylethyl hydroperoxide and 1,2,3,4-tetrahydro- 1-naphthyl hydroperoxide has been achieved by chiral HPLC on a cellulose tris(3,5-dimethylphenyl carbamate) stationary phase coated on silica gel. The method has been used to obtain several hundred milligrams of highly enriched enantiomers (%ee >98) which were characterized by (.Iu and circular dichroism spectra, respectively. Configurational assignments were achieved for 1,2,3,4-tetrahydro-1- naphthyl hydroperoxide enantiomers. o 1995 Wiley-Liss, Inc. Optically active hydroperoxides which may be used as po- tential stereoselective oxidizing reagents are of great inter- est. Some optically active hydroperoxides in which the hy- droperoxy group is attached directly to an asymmetric C-atom were obtained by photooxidation of thiazolidines, ' oxidation of 2,3-unsaturated glycosides with hydrogen peroxide, ' or by enzymatic oxidations5 and multistep syntheses from deriva- tives of polyunsaturated carbonic acids.4 The resolution of simple hydroperoxides as 1-phenylethyl hydroperoxide was successfully accomplished by liquid chromatography of diaste- reomeric derivativess or by enzymatic acylation in the pres- ence of lipases,6 by the oxidation of sulfides in the presence of chloroperoxidase, ' or quite recently by horseradish peroxi- dase-catalyzed enantioselective reduction in the presence of guaiacol. The kinetic resolution of tertiary hydroperoxides via Sharpless epoxidation of allylic alcohols9. '" yielded only moderate enantiomeric excesses. Chiral chromatography by HPLC is known to be a convenient method to provide enan- tiomers in high enantiomeric purity. '' Modified cellulose sta- tionary phases have been already successfully applied to the analytical scale enantioseparation of racemic hydroperox- ides. The present paper deals with the optical resolution of 1-cyclohexyl-1-phenylethyl hydroperoxide (CPEHPO, I) and 1,2,3,4-tetrahydro-l-naphthyl hydroperoxide (THPO, 11) on cellulose tris(3,5-dimethylphenyl carbamate) coated on a wide-pore silica support in order to obtain high enantiomeri- cally enriched samples. In addition to this the hitherto unavail- able enantiomers were subjected to chiroptical characteriza- tion.

The first total synthesis of extracellular factor, "Avenolide", in Streptomyces avermitilis has been achieved using a convergent approach. The stereogenic centers in two key segments were installed using Sharpless epoxidation and dihydroxylation. This synthetic study allowed the determination of the absolute configuration of avenolide as 4S,10R, and yielded important information on its structure-activity relationship.

Based on a retrosynthetic analysis, a concept for the synthesis of all stereoisomers of the C(1)-to-C(6) segment of phomenoic acid has been developed. Both enantiomers of the chiral synthon 9 were prepared starting from rac-epoxy-diester 10. They were converted to both enantiomers of the epoxyalcohol, 16 and 21, respectively, using Sharpless epoxydation. They served as building blocks for the synthesis of the tetrol derivatives 20 and 22, respectively. All four stereoisomers were obtained in optically pure form. They contain the correct assembly of protected functional groups, allowing selective deprotection in view of further transformations.

The kinetic resolution of tertiary hydroperoxides via catalytic Sharpless epoxidation with various allylic alcohols has been investigated. By using 1-cyclohexyl-1-phenylethyl hydroperoxide an enantiomeric excess (e.e.) of up to 29% of the resolved hydroperoxide has been observed at a consumption of the racemic hydroperoxide of nearly 50%. The e.e. can be increased, however, only by raising the hydroperoxide consumption.

The synthesis of the monoterpene (+)-artemeseole (1b) is accomplished by starting from (Z)-dienol 5. Sharpless epoxidation of 5 gives oxirane 4. Attempted opening of the epoxide ring in 4 or in derivatives 8a, b by various allyl or acetylide anions gives side reactions, but the desired coupling with a C3 unit is achieved in the reaction of silyl-protected oxirane 8b with 9 or 13 giving 17 and 19a, respectively. Alkenol 19a is further converted into oxirane 21 by desilylation, tosylation, and base-induced epoxide formation. Anion generation from 21 by reductive desulfurization yields (dialkenylcyclopropyl)methanol 3. Acid-catalyzed cyclization to a tetrahydrofuran completes the synthesis of 1b.

Advances in the field of the synthesis of optically active carotenoids are reviewed. It is shown that the main end-groups or at least precursors of them have been synthesized and that many carotenoids have been prepared in enantiomerically pure form. For the introduction of the centers of chirality selective reduction with baker's yeast, the selection of easily available, naturally occurring, optically active compounds as starting material and the Sharpless epoxidation were applied. It is also shown that many problems are still unsolved. INTRODUCTION Today, one of the main tasks of synthetic organic chemistry is the synthesis of enantiomerically pure compounds with important biological activities, particulary in view of the possibility of industrial application. In 1978 at the symposium in Madison, Dr. Mayer gave an excellent review of the synthesis of optically active carotenoids (ref. 1). The present paper is a continuation of this overview, whereby unsolved problems are also discussed; thus the work in this field during the last decade is reviewed. From the more than 560 naturally occurring carotenoids (ref. 2) about 370 are chiral and are therefore targets for synthesis in enantiomerically pure form. This includes the synthesis of carotenoids with a relative simple structure such as a-carotene bearing o n l y one chirality center, and also of neoxanthin or fucoxanthin which have five asymmetric carbon atoms plus the allenic structure. The synthesis of a carotendid in optically active form consists mainly of the synthesis of an optically active end-group or an appropriate building block, even though the synthesis of the whole carotenoid molecule may sometimes cause major problems. Therefore the main emphasis in this paper is on the synthesis of the individual end-groups. Before discussing the synthesis of or the approaches to the different end-groups, it must be pointed out that, for many natural occurring carotenoids, the structure, and this term includes the stereochemistry, is still unknown or at least uncertain and in all these cases a re-isolation, followed by structural elucidation with all the modern spectroscopic methods, especially high-resolution NMR-spectroscopy, is absolutely necessary. THE SYNTHESIS OF THE CHIRAL END-GROUPS Acyclic chiral end-groups The three main acyclic end-groups with an asymmetric carbon atom are the (R)-1,16-didehydro-I,2-dihydro-2-hydroxy-~-en~-group of aleuriaxanthin (A), the (R)or (S)-3,4-didehydro-l,2-dihydro-l,2-dihydroxy-~-end-group, which occurs e.g. in plectaniaxanthin and the (S)-l,2-dihydro-1,2-epoxy-~-end-group, which is characteristic of 1,2epoxylycopene. The synthesis of the naturally occurring (R)-aleuriaxanthin (1) and its enantiomer has been described by Eschenmoser et al. (ref. 3) (Fig. 1). Starting with Q-acetylgeraniol (2) the introduction of the chirality center was achieved by the enantioselective Sharpless epoxidation (ref. 4 ) . After opening the epoxide, the secondary hydroxyl group was protected and the double bond introduced by treatment with thionyl chloride; by standard reactions both enantiomers were synthesized. Another approach, starting from a readily available optically active synthon, was investigated in our laboratories for the synthesis of plectaniaxanthin (2) and myxol (3) (Fig. 2). Starting with either D-serine and D-mannitol or L-serine and L-mannitol, respectively, both enantiomers of the C5-building block 5 were synthesized in high yield and good optical purity (ref. 5 ) and this synthon was used for the synthesis of the Clo-phosphonium salt 6. The Wittig reaction with the appropriate C3o-aldehyde gave (S)-plectaniaxanthin ( 3 ) and (3R,Z'S)-myxol ( A ) , albeit in very low yields, due to the poor reactivity of the C30-aldehyde (ref. 6). Investigations to improve the synthesis e.g. according to the scheme CLO + C20 + C1o = C40 or C20 + C20 = C40 were unsatisfactory (ref.

An efficient stereospecific total synthesis of AZT (nine steps from crotonaldehyde) is reported in which the chirality is introduced via Sharpless epoxidation and therefore intermediates for the synthesis of both D- and L-AZT are easily produced

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids