Synthesis and absolute stereochemistry of roseophilin

The enantiospecific total synthesis of natural roseophilin has been completed in 7.0% overall yield over 15 steps by means of an asymmetric cyclopentannelation. This establishes the absolute configuration of the natural product as 22R,23R. Cyclopentenone (+)-12 was prepared in 78% yield and 86% ee in the key step.     

Synthesis and stereochemistry of tetrahydroprotoberberine derivatives

A series of 5-hydroxytetrahydroprotoberberines has been prepared from 3-aryltetrahydroisoquinoline derivatives via successive N-alkylation, oxidation and cyclization in acidic media. The relative configurations of the resulting diastereomeric 5-hydroxytetrahydroprotoberberines are reported.     

Synthesis,stereochemistry and absolute configuration of deodarols and deodarones

The stereochemistry and absolute configuration of the four deodarols and two deodarones derived from R-(+)-limonene is described.     

Synthesis and assignment of the absolute stereochemistry of (+)-hemifistularin 3

The first total synthesis of the marine natural product (+)-hemifistularin 3 in enantiomerically pure form was accomplished by using the amide forming reaction of (+)-spiroisoxazoline ester with the (+)-octopamine derivative. The stereodivergent strategy employed in this effort enabled the assignment of the absolute configurations at the three stereogenic centers in (+)-hemifistularin 3.     

Synthesis and stereochemistry of some new derivatives of cis-dihydropinol

The synthesis of four new derivatives of cis-hydroxy-cis-dihydropinol with allyl-, epoxyalkyl-, hydroxyalkyl- and ketoalkyl-groups substituted on the cyclohexane ring is presented. The cis-orientation of hydroxyl group at C-2 and the configuration of all stereogenic centers is confirmed by X-ray crystallography.     

The absolute stereochemistry of grenadamide

3-(2S-Heptylcycloprop-1S-yl)propanoic acid 2-phenylethanamide was synthesised from cis-cyclopropan-1,2-dimethanol via enzymatic desymmetrisation of the dibutyrate; it gave identical NMR spectroscopic data to those reported for grenadamide but had an equal and opposite absolute rotation, indicating that the latter is the 2R,1R-enantiomer.     

The absolute stereochemistry of crotonitenone

The configuration at C—4 of the novel casbenoid diterpene, crotonitenone (3), was determined by Horeau's method as (R) — hence the absolute stereochemistry of the molecule is as written in (3).     

Determination of the absolute stereochemistry of Etzionin

The absolute configuration of Etzionin, a marine peptide-like compound isolated in 1989 from a red tunicate collected from the Red Sea has been determined by a combination of synthetic and spectroscopic procedures. Finally, its absolute stereochemistry has been established as 3S,3′R.     

Synthesis,resolution, and absolute stereochemistry of (-)-blestriarene C

A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.     

Determination of absolute stereochemistry of panaxynol

Absolute stereochemistry of panaxynol was determined by exciton chirality method. The circular dichroism spectra of panaxynol p-bromobenzoate and p-dimethylaminobenzoate show the negative exciton chirality at λ_ext indicating the S configuration of the chiral center.     

The absolute stereochemistry of cascarillic acid

((1S,2R)-2-Hexylcycloprop-1-yl)acetic acid has been synthesised from cis-1,2-dihydroxymethylcyclopropane and shown to be identical to cascarillic acid obtained from cascarilla essential oil.     

Synthesis and stereochemistry of mono- and di-olefin derivatives of tetrairidium carbonyl clusters

The reactions of NEt₄[Ir₄(CO)₁₁Br] (I) with ethylene, cyclopropene, 5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene and bicyclo[2.2.1]hept-2-ene in the presence of AgBF₄ gave high yields of Ir₄(CO)₁₁(olefin) (II-V), in which the olefin is bonded in an axial position on a basal Ir atom. The mono-olefin in II-V is quantitatively displaced by CO giving Ir₄(CO)₁₂ or by SO₂ giving Ir₄(CO)₁₁(SO₂). The reaction of I with bicyclo[2.2.1]hepta-2,5-diene, cycloocta-1,5-diene or cyclooctatetraene in the presence of AgBF₄ gave Ir₄(CO)₁₀(η⁴-polyolefin), the first substitution taking place preferentially at an axial site giving Ir₄(CO)₁₁(η²-polyolefin), followed by chelation on a radial site of the same metal center. All the above clusters are fluxional at room temperature.     

Synthesis and stereochemistry of 2,5-dimethyltetrahydrothiopyran-4-one mono- and diacetylenic derivatives

New mono- and diacetylenic alcohols and glycols of tetrahydrothiopyran family were synthesized. Steric structures of the individual stereoisomers of these alcohols and glycols were established based on the ¹H and ¹³C NMR spectroscopic data. Stereochemistry of ethynylation of 2,5-dimethyltetrahydrothiopyran-4-one was studied.     

Total synthesis and absolute stereochemistry of plakortone E

The absolute stereochemistry of plakortone E, a cytotoxic metabolite of the Caribbean sponge, was established to be 1, by the synthesis of the racemic C-8 epimer (±)-2 and then of (−)-1 itself, which was identical with the natural compound.     

Total synthesis and absolute stereochemistry of plakortone D

The first total synthesis of plakortone D is described and thereby establishes the structure and absolute stereochemistry of the most biologically active member of the marine-derived plakortone family. The sterically congested bicyclic lactone core results from a Pd(II)-induced hydroxycyclization-carbonylation-lactonization sequence on an enediol whose chirality was installed by AD-technology. Attachment of the side chain, also constructed using AD-methodology, was achieved by using a modified Julia coupling. The described approach enables acquisition of other plakortones and analogues, in the correct (natural) stereochemical series.