A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.     

A concise and improved synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A concise and improved stereoselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is based on a Dötz benzannulation and an improved oxa-Pictet-Spengler cyclization as the key steps. The synthesis is achieved in six steps in overall yields of 18% for eleutherin and 20% for allo-eleutherin.     

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H has been achieved. Key step involved construction of all-carbon quaternary carbon by palladium-catalyzed conjugate addition of arylboronic acid to 3-methyl cyclohexenone. Furthermore, a new approach to build [6-5-6] tricyclic backbone via formyl introduction and subsequent aldol-type condensation was also explored.     

A formal synthesis of (+)-lactacystin

A synthetic route to the neurotrophic agent (+)-lactacystin has been developed utilizing a base-promoted intramolecular alkylidenecarbene C-H insertion as the key transformation.     

Total synthesis of (+)-hygrine via asymmetric phase-transfer catalytic alkylation

The first enantioselective synthesis of (+)-hygrine (1) is reported. 1 was obtained in 12 steps with 29% overall yield and 97% ee via asymmetric phase-transfer catalytic alkylation and ring-closing metathesis as key steps. The absolute configuration of (+)-hygrine could be directly confirmed as R.     

Concise formal synthesis of (+)-pyripyropene A

A concise enantioselective synthesis of A/B bicyclic segment of naturally occurring α-pyrone meroterpenoid pyripyropene A is achieved in 9 steps (LLS) and 7.5% yield starting from R-(?)-carvone. The significant points of the synthesis include: (1) an intramolecular 1, 3-dipolar cycloaddition reaction to construct the A ring and assemble C4 quaternary carbon stereocenter as well; (2) reductive cleavage of the oxazole motif utilized Raney Ni/B(OCH₃)₃.     

A facile asymmetric synthesis of (+)-eldanolide

The monoterpenoid pheromone (+)-eldanolide, a long range sex attractant, has been synthesized in four steps from the chiral 2,3-epoxy alcohol 4 in 36% overall yield. Our synthetic strategy features the formation of a 1,3-diol by regio- and stereoselective ring opening of 2,3-epoxy alcohol 4, an intermediate easily available from Sharpless asymmetric epoxidation. Other key steps include one carbon elongation, saponification, and lactonization. The present work constitutes a general method for the rapid synthesis of a number of related γ-lactone natural products.     

A six-step asymmetric synthesis of (+)-hyperaspine

[reaction: see text] The ladybird alkaloid, (+)-hyperaspine, has been synthesized in a concise and highly stereoselective manner. The total synthesis was accomplished in six steps and 21% overall yield.     

A total asymmetric synthesis of (+)-ar-turmerone

Employing a chiral oxazoline, a total synthesis of the title compound is described.     

Concise formal synthesis of (+)-neopeltolide

A concise formal synthesis of (+)-neopeltolide (1) has been accomplished. The synthesis demonstrated high atom efficiency employing only one step of functional group protection. Key steps involved iridium-catalyzed double asymmetric carbonyl allylation, palladium-catalyzed intramolecular alkoxycarbonylation, ruthenium-catalyzed olefin isomerization, and ring-closing metathesis.     

An asymmetric formal synthesis of fasicularin

An asymmetric formal synthesis of fasicularin (1) is described. This natural product, isolated from the extracts of the marine invertebrate Nephteis fasicularis, has shown modest cytotoxicity towards Vero cells. Fasicularin is among only two members of the cylindricine family of natural products, along with lepadiformine (2), to possess a trans A-B ring junction. Key steps of this approach to 1 involve a siloxy-epoxide semipinacol rearrangement of 5 to 6, a B-alkyl Suzuki-Miyaura coupling reaction by using enol trifluoromethanesulfonate 19 and a substrate-directed hydrogenation reaction of 24. This formal synthesis also highlights the difficulty in the incorporation of the thiocyanate functionality present in 1.     

A formal convergent synthesis of (+)-trans-solamin

A formal convergent synthesis of solamin is disclosed. The synthetic strategy exploits the potential of the sulfinyl group as an auxiliary, nucleophile and in C-C bond formation. The synthetic route can be adapted to the synthesis of stereoisomers of solamin, analogs with variable carbon side chains, and other members of mono-THF acetogenins.     

Enantioselective formal synthesis of antitumor agent (+)-ottelione A

The enantioselective formal synthesis of a natural antitumor product, (+)-ottelione A, was achieved through a catalytic enantioselective Diels-Alder strategy. These endeavors have led to the synthesis of a variety of synthetic analogues of this biologically potent natural product.     

A concise asymmetric total synthesis of (+)-brevisamide

A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide.     

One-pot, catalytic, asymmetric synthesis of polypropionates

[reaction: see text] The opening of methylketene dimer, followed by aldol reactions of the resulting enolate, provides a convenient access to syn,syn-dipropionate aldol adducts of a variety of aldehydes. These aldol adducts are useful precursors in the synthesis of complex polypropionates.     

Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction

A catalytic process for the synthesis of optically active C4-substituted tetrahydroindandiones using an asymmetric intramolecular aldol condensation reaction was developed. When 30 mol% of phenylalanine and 50 mol% of pyridinium p-toluenesulfonate were used under highly concentrated conditions, a variety of C4-substituted tetrahydroindandiones and octahydronaphthalenediones were obtained in high yield (up to 89% yield) and high enantiomeric excess (up to 94% ee). One of the products was successfully transformed into the key intermediate for the synthesis of the phosphatidylinositol 3-kinase inhibitor wortmannin, achieving formal total synthesis of (+)-wortmannin.     

Stereoselective formal total synthesis of (+)-methynolide

A highly stereoselective and convergent formal total synthesis of (+)-methynolide is described. The salient features of this synthesis have been the construction of the C1-C7 and C8-C11fragments via a desymmetrization approach, Sharpless asymmetric epoxidation of an allyl alcohol, respectively, and linkage of both the fragments by Nozaki-Hiyama-Kishi reaction.     

An asymmetric synthesis of (+)-kjellmanianone

Racemic and asymmetric syntheses of kjellmanianone, a novel cyclopentenoid antibiotic, are described.