Enantioselective total syntheses of (+)-arborescidine A, (-)-arborescidine B, and (-)-arborescidine C

Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)-arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine (7). The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro-beta-carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro-beta-carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Pa?s and co-workers, and are counter to their recently revised assignment.     

Enantioselective total syntheses of (-)-clasto-lactacystin beta-lactone and 7-epi-(-)-clasto-lactacystin beta-lactone

An alkylidene carbene 1,5-CH insertion has been used as a key step in an efficient enantioselective total synthesis of (-)-clasto-lactacystin beta-lactone, and its C7-epimer. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester.     

Enantioselective syntheses of (-)- and (+)-monomorine I

A concise enantioselective total synthesis of unnatural (-)-monomorine I has been achieved starting from lactam 2 in 54% overall yield. Natural (+)-monomorine I was also synthesized.     

Enantioselective syntheses of (S)- and (R)-8,9-dihydroxydihydromagnolol

8,9-Dihydroxydihydromagnolol 5 was synthesized in four steps in which the synthesis of magnolol 4 was improved and the absolute configuration of 5 was confirmed as (R).     

Asymmetric total syntheses of (-)-variabilin and (-)-glycinol

Total syntheses of (-)-variabilin and (-)-glycinol have been accomplished, using the catalytic, asymmetric "interrupted" Feist-Be?nary reaction (IFB) as the key transformation to introduce both stereogenic centers. A monoquinidine pyrimidinyl ether catalyst affords the IFB products in over 90% ee in both cases. Other key steps include an intramolecular Buchwald-Hartwig coupling and a nickel-catalyzed aryl tosylate reduction.     

Enantioselective total synthesis of (-)-dactylolide

[reaction: see text] The enantioselective total synthesis of (-)-dactylolide is reported. The absolute stereochemistry of the tetrahydropyran was established by catalytic asymmetric Jacobsen hetero-Diels-Alder reaction. The remote C19 stereocenter was introduced by a sequence of chelation-controlled Grignard addition and Ireland-Claisen rearrangement.     

Enantioselective total synthesis of (-)-laurenditerpenol

A highly convergent total synthesis of (-)-laurenditerpenol has been accomplished through an organolithium to aldehyde nucleophilic addition. Preparation of the prerequisite key intermediates in optically pure form was based on an improved, short, and efficient synthesis of "wine lactone" from (S)-limonene and Corey's catalytic enantioselective Diels-Alder reaction of 2,5-dimethyl furan with diethyl fumarate.     

Enantioselective total syntheses of ropivacaine and its analogues

An alternative asymmetric synthesis of ropivacaine and analogues employing the ‘cation pool’ strategy and host/guest supramolecular co-catalysis approach is presented. In this study, chiral auxiliaries, several soft nucleophiles as well as one-pot conditions for anodic oxidation, followed by nucleophilic addition, have been applied.     

Enantioselective total syntheses of trichodermamides A and B

Starting from commercially available (-)-quinic acid, the enantioselective total syntheses of trichodermamides A and B were achieved. The key reactions involve the stereoselective construction of the oxazine ring via an intramolecular epoxide ring opening reaction and an EDCI-assisted peptide coupling reaction.     

Enantioselective total synthesis of (-)- and (+)-petrosin

The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki-Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.     

Enantioselective total syntheses of omuralide, 7-epi-omuralide, and (+)-lactacystin

An alkylidene carbene 1,5-CH insertion has been used as a key step in an enantioselective total syntheses of omuralide, its C7-epimer, and (+)-lactacystin. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester.     

Enantioselective total synthesis of (-)-clavosolide B

Enantioselective synthesis of 2, a revised structure for (-)-clavosolide B, was accomplished by a convergent approach, where syn-selective aldol, hydroxy-directed cyclopropanation, Mitsunobu inversion, Schmidt-type glycosylation, and macrolactonization reactions were utilized as key reactions. Comparison of 1H and 13C NMR spectra and optical rotation measurement confirmed the relative and absolute stereochemistry of clavosolide B (2).     

Enantioselective total synthesis of (-)-xialenon A

The first total synthesis of (-)-xialenon A (1) via conjugate allylation of a 1,5-cyclooctadiene-derived bicyclo[3.3.0]octenone 3 and an alpha'-hydroxylation on the more hinderd face of enone 9 using hypervalent iodine chemistry, is described.     

Enantioselective total synthesis of (-)-kibdelone C

The kibdelones are aromatic polyketide natural products featuring isoquinolinone and tetrahydroxanthone ring systems. They display potent cytotoxicity toward a range of human cancer cell lines. Here, we present an enantioselective total synthesis of kibdelone C that utilizes a Shi epoxidation to establish the absolute and relative stereochemistry, an acid-catalyzed cyclization to form the tetrahydroxanthone, and a C-H arylation to complete the hexacyclic skeleton.     

Enantioselective total synthesis of (-)-heliannuol A

An efficient and enantiocontrolled total synthesis of (-)-heliannuol A has been accomplished by employing ring closing metathesis and sequential diastereoselective epoxidation and regioselective reductive cleavage of the epoxide ring.