An asymmetric approach to the synthesis of trans-dihydrindandione

A three-step asymmetric approach to the synthesis of (3aS,7aS)-3a,4-dihydro-7a-methyl-1,5(7aH)-indandione in 60% enantiomeric excess is described.     

Application of an intramolecular dipolar cycloaddition to an asymmetric synthesis of the fully oxygenated tricyclic core of the stemofoline alkaloids

An intramolecular non-stabilized azomethine ylide dipolar cycloaddition was applied toward the first non-racemic synthesis of the fully oxygenated bridged pyrrolizidine core (45) of (+)-stemofoline (1) in 11 steps from a commercially available starting material.     

An asymmetric approach to spirocylic systems: a formal synthesis of zizaene

A general route to enantiopure spirocarbocycles is described. The use of various chiral bicyclic lactams 1 that have been doubly alkylated with olefinic halides gives good yields of alpha,alpha-disubstituted chiral lactams 2 which were cyclized to spiro-olefins using ring closure metathesis methodology (Grubbs' catalyst). These spirolactams 3, formed in generally excellent yields, were shown to be smoothly transformed into spirocyclopentenone 6, spirocyclohexenone, 7, and spirolactams 8. Further demonstration of this spirocyclization methodology was featured in a formal synthesis of zizaene, by preparing in enantiomeric form the Coates' intermediate 21. This synthetic effort provided additional examples of the synthetic versatility of chiral bicyclic lactams 2a,b.     

De novo asymmetric synthesis of milbemycin beta3 via an iterative asymmetric hydration approach

The enantioselective synthesis of the spiroketal/macrolide natural product milbemycin beta3 has been achieved in 22 steps and 2.8% overall yield from an achiral dienoate. The spiroketal ring system was installed by three sequential asymmetric hydrations followed by sprioketalization. Both the absolute and relative stereochemistry of milbemycin beta3 was introduced by two Sharpless asymmetric dihydroxylations, two pi-allylpalladium-catalyzed reductions, and an iridium-catalyzed hydrogen migration/Claisen rearrangement to install the C-12 stereocenter.     

Total synthesis of (+)-laurencin: an asymmetric alkylation-ring-closing metathesis approach to medium ring ethers

[formula: see text] The enantioselective total synthesis of (+)-laurencin 1 is achieved in 18 steps from (S)-(+)-4-benzyl-3-benzyloxyacetyl-2-oxazolidinone. The key steps in this synthesis are an asymmetric glycolate alkylation leading to acyl oxazolidinone 2 and a subsequent ring-closing olefin metathesis to construct the oxocene core of 1. The approach to medium ring ethers utilized in this synthesis provides a general and efficient route to the cyclic core of other marine natural products.     

A diastereoselective approach for an asymmetric synthesis in pinnaic acid series

An enantiopure spiran-bearing advanced intermediate in pinnaic acid series was obtained in 11 steps starting with CN(R,S) building block.     

An asymmetric synthesis of L-pyrrolysine

An efficient asymmetric synthesis of the 22nd amino acid L-pyrrolysine has been accomplished. The key stereogenic centers were installed by an asymmetric conjugate addition reaction. A Staudinger/aza-Wittig cyclization was used to form the acid-sensitive pyrroline ring. Pyrrolysine was synthesized in 13 steps in 20% overall yield.     

Furanophane transannular Diels-Alder approach to (+)-chatancin: an asymmetric total synthesis of (+)-anhydrochatancin

(+)-anhydrochatancin was synthesized while attempting an enantioselective total synthesis of (+)-chatancin. The presented route constitutes the furanophane approach, one of the two ways of proposed biosynthesis which may involve transannular Diels-Alder (TADA) reaction to link this diterpene biogenetically to the furanocembranoids. Highlights of the synthetic work include the assembly of chiral, acyclic, trisubstituted furan 28 via a coupling of aldehyde 10 and dilithiofuroic acid 11, a macrocyclization to furanophane 29E via ring-closing metathesis, a TADA reaction to reach tetracyclic intermediate 4, and a hydride shift mediated oxygen transposition as a final rearrangement to the target. Unfortunately, the strongly acidic condition required for the last step allows only the isolation of anhydrochatancin 30 due to the acid sensitivity of chatancin 1.     

Expedient approach to chiral cyclobutanones: asymmetric synthesis of cyclobut-G

An efficient one-pot asymmetric synthesis of cyclobutanones from chiral enol ethers is described. The approach is illustrated with alkyl- and functionalized alkyl-substituted enol ethers (nine examples). A new enantioselective synthesis of cyclobut-G (Lobucavir) could thus be achieved.     

An aldol-based approach to the asymmetric synthesis of L-callipeltose, the deoxyamino sugar of L-callipeltoside A

[reaction: see text] The L-callipeltose subunit of L-callipeltoside A has been synthesized in 10 steps and 13% overall yield from D-threonine. The key steps are a highly diastereoselective Felkin anti aldol addition to a methyl ketone and a selective methylation of a secondary alcohol in the presence of a secondary carbamate.     

Diastereoselective synthesis of 2-substituted-piperidin-4-ones as convenient precursors for an asymmetric approach to carbacephams

Optically active carbacephams can be efficiently prepared generating the β-lactam ring on 2-substituted-piperidin-4-ones. These can, in turn, be prepared diastereoselectively through a Michael-Michael reaction sequence initiated by benzylamine on precursors derived by Wittig reaction between serinals and 4-[(4-methylphenyl)sulfonyl]-1-(triphenylphosphoranylidene)-2-butanone.     

Formal total synthesis of (+)-trehazolin. Application of an asymmetric aldol-olefin metathesis approach to the synthesis of functionalized cyclopentenes

An asymmetric synthesis of the aminocyclopentitol pseudosugar of trehazolin has been completed. The synthesis hinges on an asymmetric aldol-ring closing metathesis strategy to construct the five-membered ring with control of both the relative and absolute stereochemistry.     

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.     

An asymmetric synthesis of (+)-kjellmanianone

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

An efficient asymmetric synthesis of grenadamide

The cyclopropane containing natural product grenadamide has been prepared in six steps using (R)-5,5-dimethyl-oxazolidin-2-one as a chiral auxiliary for asymmetric synthesis. Key synthetic steps include the use of the β-hydroxyl group of a syn-aldol product as a ‘temporary’ stereocentre to control the facial selectivity of a directed cyclopropanation reaction, as well as the use of phenylethylamine as a nucleophile for the direct aminolysis of an N-acyl-oxazolidin-2-one intermediate.     

An expedient asymmetric synthesis of platencin

A short and efficient synthesis of enone 3, a key intermediate in the total synthesis of platencin (2), based on an intramolecular Diels-Alder reaction is described.     

An asymmetric synthesis of (+)-desoxoprosophylline

An efficient synthesis of (+)-desoxoprosophylline is described. The key steps in the reaction sequence include the preparation of an N-Cbz-sulfilimine from the corresponding sulfoxide using the Burgess reagent, regio- and stereoselective hetero-functionalization of an alkene using the pendant sulfilimine as the nucleophile and a stereoselective amidomercuration to form the cis-2,6-disubstituted piperidine ring.     

An asymmetric synthesis of sulfobacin A

A facile synthesis of sulfobacin A has been developed starting from (R)-cyclohexylideneglyceraldehyde (11). The key steps in the synthesis are the highly diastereocontrolled allylation of 11 and syn-selective reduction of a ketone derived from 11. The other attractive features are the operational simplicity and the use of inexpensive compounds/reagents.