A concise and stereoselective synthesis of (+)- and (−)-deoxoprosophylline

An efficient synthesis of (+)- and (−)-deoxoprosophylline was accomplished from the readily available cis-2-butene-1,4-diol in which the Sharpless asymmetric dihydroxylation was used as the key step.     

Synthesis of polyhydroxylated indolizidines and piperidines from Garner's aldehyde: total synthesis of (−)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine,pentahydroxy indolizidines, (−)-1-deoxynojirimycin, (−)-1-deoxy-altro-nojirimycin,and related diversity

Diastereoselective and diverse synthesis of polyhydroxylated indolizidines and piperidines have been described, where a common chiral intermediate 2-(hydroxymethyl) piperidine-3-ol is converted into (−)-swainsonine, (+)-1,2-di-epi-swainsonine, (+)-8,8a-di-epi-castanospermine, pentahydroxy indolizidines, (−)-1-deoxynojirimycin, (−)-1-deoxy-altro-nojirimycin, and related diversity. The key steps were hydroxy directed intramolecular aminomercuration, Mitsunobu cyclization, and diastereoselective dihydroxylation.     

Chiral vicinal diols as platforms for separable diastereomers in Johnson-Claisen rearrangement: a new short route to (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide

The chiral vicinal diols prepared by asymmetric dihydroxylation in high enantioselectivities provide an excellent platform for separable diastereomers in the Johnson-Claisen rearrangement. The separated syn-diastereomers were converted into the advanced γ-(lactone-lactol) intermediates (in six steps, 26-27% overall yields) for the synthesis of (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide.     

Stereoselective total syntheses of (+)-exo- and (−)-exo-brevicomins, (+)-endo- and (−)-endo-brevicomins, (+)- and (−)-cardiobutanolides, (+)-goniofufurone

Stereoselective total syntheses of aggregation pheromones (+)-exo-brevicomin (9a), (−)-exo-brevicomin (9b), (+)-endo-brevicomin (9c), (−)-endo-brevicomin (9d) and styryllactones (+)-cardiobutanolide (14a), (−)-cardiobutanolide (14b), and (+)-goniofufurone (19a) were achieved in good yields from enantiomerically pure highly functionalized furanoid glycal building blocks (1a-d) involving similar synthetic strategies, thus making these furanoid glycals highly useful building blocks in diversity-oriented synthesis (DOS).     

The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″

The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.     

Asymmetric synthesis of (−)-acaterin

The asymmetric synthesis of (−)-acaterin, an inhibitor of acyl-CoA cholesterol acyl transferase has been achieved starting from the commercially available starting materials, octan-1-ol and methyl (R)-lactate. The key steps are a Sharpless asymmetric dihydroxylation and a Wittig olefination.     

An efficient stereoselective synthesis of (2S,4S,5R)-(−)- and (2R,4R,5S)-(+)-bulgecinine

A short synthetic route to (−)-and (+)-bulgecinine, the amino acid moiety of the bulgecins was achieved from the readily available nonchiral pool starting material cis-2-butene-1,4-diol in which a Claisen orthoester rearrangement and a Sharpless asymmetric dihydroxylation were used as the key steps.     

Total synthesis of (+)-epiepoformin and (−)-phyllostine

An efficient asymmetric total synthesis of naturally occurring cyclohexeneoxides, (+)-epiepoformin and (−)-phyllostine has been achieved using the chiral building block available from the base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone. Since (−)-theobroxide was derived from the same precursor of (+)-epiepoformin, the formal total synthesis of (−)-theobroxide has also been achieved.     

Gold catalysis in stereoselective natural product synthesis: (+)-linalool oxide, (−)-isocyclocapitelline, and (−)-isochrysotricine

A stereoselective synthesis of the tetrahydrofuran-containing natural products (2S,5R)-(+)-linalool oxide (1), (−)-isocyclocapitelline (2), and (−)-isochrysotricine (3) is reported. Key steps are the copper-mediated S_N2′-substitution of propargyl oxiranes 7 and the gold-catalyzed cycloisomerization of dihydroxyallenes 8/17, resulting in a highly efficient center-to-axis-to-center chirality transfer. The enantioselective total synthesis of (−)-isocyclocapitelline (2) and (−)-isochrysotricine (3) allowed the elucidation of the absolute configuration of these β-carboline natural products.     

Highly stereoselective and stereospecific syntheses of a variety of quercitols from d-(−)-quinic acid

The highly stereoselective synthesis of (−)-epi-, (−)-allo- and neo-quercitols as well as stereospecific synthesis of (−)-talo- and (+)-gala-quercitols have been achieved. The general strategy is employing dihydroxylation of the isolated double bond of various kinds of protected chiral (1,4,5)-cyclohex-2-ene-triols, which are derived from d-(−)-quinic acid. The choosing of protecting groups from either BBA (butane 2,3-bisacetal) or acetyl groups will result in the various degrees of stereoselectivity of dihydroxylation. On the other hand, the cyclohexylidene acetal moiety is attributed to the stereospecificity during dihydroxylation to afford the request molecules.     

Stereoselective synthesis of (−)-cytoxazone and (+)-epi-cytoxazone

Optically pure (−)-cytoxazone was synthesized, starting from methyl p-methoxycinnamate, in six steps and in 31% overall yield. The required anti-aminoalcohol configuration was established by combining Sharpless asymmetric aminohydroxylation with the configurational inversion of the intermediate amidoalcohol via an oxazoline. The synthesis of (+)-epi-cytoxazone is also described.     

A chemoenzymatic synthesis of the linear triquinane (−)-hirsutene and identification of possible precursors to the naturally occurring (+)-enantiomer

An enantiomerically pure cis-1,2-dihydrocatechol, which is readily obtained via a toluene dioxygenase-mediated dihydroxylation of toluene in a whole-cell biotransformation process, has been converted over 17 steps into the linear triquinane (−)-hirsutene. Since the enantiomer of the starting material is also available this work constitutes a formal total synthesis of the naturally occurring (+)-form of hirsutene. Furthermore, minor modifications of the route used here offer the possibility of accessing (+)-hirsutene from the original starting material.     

Stereoflexible total synthesis of (−)-epiquinamide

Hydroxy propiolate rearrangement to conjugated diene, Sharpless asymmetric dihydroxylation and one-pot quinolizine construction have been used as key steps in the total synthesis of (−)-epiquinamide.     

Stereoselective total synthesis of (+)-varitriol

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d-(−)-ribose and ethyl (S)-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels-Alder reaction.     

Enantioselective total synthesis of epoxyquinone natural products (−)-phyllostine, (+)-epoxydon, (+)-epiepoxydon and (−)-panepophenanthrin: access to versatile chiral building blocks through enzymatic kinetic resolution

A new enzyme mediated protocol to access versatile chiral building blocks for the synthesis of epoxyquinone natural products is delineated. Total syntheses of (−)-phyllostine, (+)-epoxydon, (+)-epiepoxydon and (−)-panepophenanthrin have been accomplished to demonstrate the efficacy of this approach.     

A short and efficient asymmetric synthesis of (−)-frontalin, (−)-exo-isobrevicomin and a volatile contributor of beer-aroma

The natural products, (−)-frontalin and (+)-exo-isobrevicomin were synthesized employing Sharpless asymmetric epoxidation and ZrCl₄-catalyzed intramolecular acetalization as the key steps. (−)-Frontalin was synthesized in three steps with a 61.4% overall yield and 89.9% ee and (−)-exo-isobrevicomin also obtained in an overall satisfactory yield of 10.1% and 97% ee. We have also synthesized the volatile contributor of beer aroma in a 96% ee.     

Enantioselective synthesis of (−)-α-conhydrine via cyclic sulfate methodology

An asymmetric synthesis of (−)-α-conhydrine is described using the Sharpless asymmetric dihydroxylation and the regiospecific nucleophilic opening of a cyclic sulfate as the key steps.     

Total syntheses of (+)- and (−)-syringolides 3 and of (+)- and (−)-syributins 1, 2 and 3

The first total syntheses of (−)-syringolide 3, (+)-syributin 3 and their unnatural enantiomers (+)-syringolide 3 and (−)-syributin 3 using a common intermediate as starting material are described. In addition, total syntheses of (−)- and (+)-syributins 1 and 2 were accomplished by means of the same methodology.     

Efficient total synthesis of (+)-exo-, (−)-endo-brevicomin and their derivatives via asymmetric organocatalysis and olefin cross-metathesis

The catalytic enantioselective synthesis of (+)-exo-, (−)-endo-brevicomin and their derivatives is described herein. This approach involves the use of the organocatalyzed asymmetric α-aminoxylation of aldehyde, in situ indium mediate allyation and olefin cross-metathesis. This versatile strategy allows for the rapid synthesis of other members of this class of natural products.     

Enantioselective synthesis of (−)-galantinic acid

An efficient enantioselective synthesis of (−)-galantinic acid 1, a non-proteogenic amino acid is described using Sharpless asymmetric epoxidation, dihydroxylation and the regioselective nucleophilic opening of a cyclic sulfite as the key steps.