Stereoselective Total Synthesis Research Articles

Development of an Amino Acid/Hydroxy Oxime Dual Catalyst System for Highly Stereoselective Direct Asymmetric Aldol Reactions in the Presence of Water

An eco-friendly dual catalyst system for stereoselective aldol reactions in the presence of water is described. It is based on the cooperative action of acyclic amino acids and H-bond donating hydroxy oxime catalysts. The synthetic utility of this dual catalyst system was further demonstrated by applying it as the key step in the expeditious and highly stereoselective total synthesis of d -lyxo-phytosphingosine (29% overall yield). Here the amino acid/hydroxy oxime system significantly accelerated the direct aldol reactions in the presence of water as compared to organic solvents. The stereo- and chemoselectivity were also significantly increased.

Stereoselective total synthesis of sphingolipids

A novel sphingosine, 1,2-diacetyl D-erythro-sphinganine having a characteristic almond flavour was isolated from the edible mushroom Grifola gargal. We have synthesized this sphinganine along with the three other sphingolipids, such as 1,2-diacetyl L-threo-sphinganine, D-erythro-sphinganine triacetate and L-threo-sphinganine triacetate using Garner aldehyde as the starting material involving the Grignard reaction and Mitsunobu inversion. The sphingolipids 1,2-diacetyl D-erythro-sphinganine and 1,2-diacetyl L-threo-sphinganine have been synthesized for the first time.

Biomimetic Synthesis of Urukthapelstatin A by Aza‐Wittig Ring Contraction

Marine bacteria produce highly cytotoxic polyheterocyclic cyclopeptide natural products by ribosomal peptide biosynthesis. Among them, urukthapelstatin A features a chain of five 2,4′‐connected azole rings within a cyclo‐octapeptide framework. We report a novel synthesis design that uses only α‐amino acids as starting materials that leads to an efficient and stereoselective total synthesis of urukthapelstatin A. Kinetically favored macro‐thiolactonization and high‐yielding aza‐Wittig heterocyclization to contract the macrocycle were crucial for success. These investigations additionally uncovered the unsuspected configurational lability of the embedded enamide substructure in solution.

Chiral approach to total synthesis of phytotoxic and related nonenolides: (Z)-isomer of (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone, herbarumin-III and their C-9 epimers

A new and efficient strategy has been developed for the stereoselective total synthesis of nonenolides: (Z)-isomer of (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone, herbarumin-III and their C-9 epimers starting from d (−) ribose. The synthesis includes the coupling of the alcohol and acid fragments of the molecules, employing Yamaguchi esterification protocol followed by intramolecular ring closure metathesis. The method has efficiently constructed the 10-membered lactone skeleton of the compounds with proper stereogenic centers containing appropriate functionalities.

First Stereo Selective Total Synthesis of Antimicrobial Trichoderic acid

AbstractThe first stereo selective total synthesis of the antimicrobial sesquiterpene trichoderic acid is reported. The key steps of this synthetic strategy involves (R)‐CBS‐mediated stereoselective keto reduction, Horner–Wadsworth–Emmons (HWE) olefination was employed twice for chain elongation, requisite aldehyde to perform HWE olefination was prepared from commercially available 3‐methylcyclohexenone and intramolecular oxa Michael addition.

ChemInform Abstract: Stereoselective Total Synthesis of Cryptomoscatone F1.

A concise stereoselective total synthesis of cryptomoscatone F1 has been accomplished by utilization of asymmetric acetate aldol reaction, Brown’s asymmetric allylation, and olefin cross-metathesis as key transformations.

Chemoenzymatic Total Synthesis of (+)-Galanthamine and (+)-Narwedine from Phenethyl Acetate.

The stereoselective total synthesis of unnatural (+)-galanthamine starting from phenethyl acetate is described. Chirality was introduced via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis-cyclohexadi-enediol, configuration of which provided the absolute stereochemistry of the ring C of (+)-galanthamine. Intramolecular Heck cyclization was used to form the quaternary carbon and dibenzofuran functionality. The synthesis of (+)-galanthamine was completed in a total of ten steps and an overall yield of 5.5 %. Experimental and spectral data are provided for all new compounds.

Stereoselective Chirality Extension of syn,anti- and syn,syn-Oxazine and Stereochemical Analysis of Chiral 1,3-Oxazines: Stereoselective Total Syntheses of (+)-1-Deoxygalactonojirimycin and (-)-1-Deoxygulonojirimycin.

This paper describes the stereoselective total syntheses of (+)-1-deoxygalactonojirimycin and (-)-1-deoxygulonojirimycin via new chiral building blocks syn,anti,syn-oxazine 11a and syn,syn,anti-oxazine 13a. These were accomplished in four steps in 44.1 and 33.7% overall yields, respectively. These chirons were derived from the stereoselective addition of a nucleophile to the corresponding aldehydes of syn,anti-oxazine 10 and syn,syn-oxazine 12. Furthermore, this paper describes the stereochemical analysis of three types of chiral 1,3-oxazines; anti,syn-, syn,anti-, and syn,syn-oxazines using the NOESY technique.

Stereoselective total synthesis of palmyrolide A via intramolecular trans N-methyl enamide formation

The stereoselective total synthesis of palmyrolide A was accomplished through macrocyclization reaction involving trans enamide formation by coupling of vinyl iodide with secondary amide in an intramolecular fashion. The two coupling partners, vinyl iodide 4 and secondary amide 3 were synthesized from the same intermediate alcohol 5. Yamaguchi esterification and CBS-reduction are the other key steps involved in the synthesis.

Stereoselective Total Synthesis of (±)-Dasycarpidol and (±)-Dasycarpidone

The protecting-group-free and scalable total syntheses of (±)-dasycarpidol and (±)-dasycarpidone, as well as the formal total synthesis of (±)-uleine, are presented starting from a common tetrahydrocarbazole-fused lactone that is conveniently prepared on multigram scale. The key azocino[4,3-b]indole skeleton is constructed via the DDQ-mediated dehydrogenative cyclization of a tetrahydrocarbazole derivative possessing an amide side chain. The syntheses of the target natural products are accomplished in high yields and in a few steps by employing readily available conventional reagents.

A facile approach for the total synthesis of neurotrophic diyne tetraol petrosiol A and petrosiol E

The first total synthesis of neurotrophic diacetylenic tetraol, petrosiol A and stereoselective total synthesis of petrosiol E was accomplished. The total synthesis involves Cadiot-Chodkiewicz coupling reaction as the key step for petrosiol A. The diastereorich chiral alcohol (third chiral center) was synthesized from CBS mediated stereoselective ketone reduction reaction for petrosiol E. Of the three chiral centers, the two chiral centers are originated from (+)-diethyl l-tartrate and the third chiral center was generated by an addition reaction of lithium trimethylsilylacetylide leading to two diastereomers which were used for the synthesis of both the natural products and their diastereomer C6-epi-petrosiol A and C6-epi-petrosiol E, respectively.

ChemInform Abstract: Stereoselective Total Synthesis of Unnatural (+)‐Anisomycin.

Stereoselective total synthesis of unnatural (+)-anisomycin from d -glucose has been achieved with an overall yield of 23%. The key synthetic features are regioselective opening of an epoxide, azidation of the resulting alcohol, and finally one-pot hydrogenation leading to cyclization to the pyrrolidine ring in a single step.

Stereoselective Synthesis of (+)‐Petromyroxol

The stereoselective total synthesis of (+)‐petromyroxol, isolated from the water conditioned with the larval sea lamprey has been accomplished by employing the cross‐metathesis, tandem Sharpless asymmetric dihydroxylation/SN2 cyclization, and regioselective ring opening of epoxide as the key steps.

Protecting-Group-Free Total Synthesis of 8-Methoxygoniodiol

A concise stereoselective total synthesis of the naturally occurring styryl lactone 8-methoxygoniodiol in five simple steps from readily available inexpensive trans-cinnamaldehyde is described. The efficient synthesis features a successful protecting-group-free strategy, with desirable step- and atom-economy. The synthetic strategy relies on a Maruoka asymmetric allylation, an epoxidation, a ring-closing metathesis, and a stereoselective epoxide ring opening as key steps.

A concise stereoselective total synthesis of decarestrictine J

In this communication, a concise and efficient synthetic route for the synthesis of decarestrictine J in enantioselective way has been described. In this synthesis, Yamaguchi esterification and ring closing metathesis (RCM) for macrocyclic ring formation have been applied as key steps.

A Total Synthesis of (–)‐Nardoaristolone B

A stereoselective total synthesis of (–)‐Nardoaristolone B, a nor‐aristolane sesquiterpenoid natural product with an unusual 3/5/6 tricyclic ring system is described. The highlights of the present work includes use of (+)‐(R)‐Pulegone as a chiral‐pool starting material, ring‐closing metathesis, allylic oxidation and stereoselective cyclopropanation. In addition, a new analogue of Nardoaristolone B (minor product from the final step) was isolated in pure form and fully characterized with the help of single‐crystal X‐ray analysis.

Total Syntheses of (+)-Marrubiin and (−)-Marrulibacetal

A stereoselective total synthesis of (+)-marrubiin has been accomplished starting from a chiral building block via the CyNH2-promoted Pauson-Khand reaction (PKR) followed by oxidative cleavage of the resultant cyclopentenone ring. Two successive oxidations and internal transacetalization culminated in the total synthesis of the antispasmodic labdane diterpenoid (-)-marrulibacetal.

First Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine.

The first regio- and stereoselective total synthesis of the axially chiral 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (1) and ancistrotectorine (2) has been described. Both possess a 7,3'-coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis-array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the "lactone method": the two molecular halves, which were activated in an "inverse-halogenated" form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold.

Carbohydrate-Based Studies Toward the Synthesis of Hamigeromycin E: A Stereoselective Total Synthesis of an Isomer of Zeaenol

A stereoselective synthesis of 14-membered macrolide hamigeromycin E (6) has been studied by employing ortho-lithiated formylation, Barbier allylation, Julia–Kocienski olefination, Mitsunobu esterification, and ring-closing metathesis (RCM) reactions. The final RCM reaction did not provide the target molecule. This study has prompted us to synthesize a stereoisomer of zeaenol and accomplish the total synthesis with the above protocols.

Short Stereoselective Synthesis of (+)-Monocerin via a Palladium-Catalysed Intramolecular Alkoxycarbonylation

A concise stereoselective total synthesis of (+)-monocerin has been accomplished using cross metathesis, tandem dihydroxylation-SN2 cyclisation and intramolecular alkoxycarbonylation as key steps. Cross-metathesis of 2-iodo-3,4,5-trimethoxyvinylbenzene and ( R)-hepten-4-ol, followed by tandem dihydroxylation-SN2 cyclisation generated a tri-substituted tetrahydrofuran ring. Finally, the dihydroisocoumarin was obtained by an intramolecular alkoxycarbonylation. In this paper, we have developed an expedient operationally simple Pd(OAc)2/bathocuproine catalysed alkoxycarbonylation under atmospheric pressure of carbon monoxide. The catalytic system developed here can be useful for the synthesis of various dihydroisocoumarins and phthalides.