An enantioselective total synthesis of (S)-(−)-licochalcone E: determination of the absolute configuration

The absolute configuration of (−)-licochalcone E (1) was determined to be (S) via the first enantioselective total synthesis of the compound. The chirality in (S)-(−)-licochalcone E (1) was installed by asymmetric methylation of the Evans' oxazolidinone derivatives.     

Synthesis of a novel sphingosine kinase inhibitor (−)-F-12509A and determination of its absolute configuration

The synthesis of a novel sphingosine kinase inhibitor, (−)-F-12509A ((−)-1), was achieved in a highly efficient manner that included nine longest linear steps and 45% overall yield from (−)-bicyclic β-ketoester (−)-2, and its absolute configuration was determined to be (5S,9S,10S).     

Synthesis to determine the absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea

The absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea, was determined to be R by synthetic studies.     

Study on the absolute configuration of (−)-palau’amine

The absolute stereochemistry of the immunosuppressive pyrrole-imidazole alkaloid (−)-palau’amine from the marine sponge Stylotella aurantium is analyzed by CD spectroscopy. With the help of a series of model compounds it is shown that the CD spectrum of (−)-palau’amine can be explained based on the assumption that the pyrrolopyrazinone partial structure is planar in 2,2,2-trifluoroethanol (TFE). Surprisingly, the natural product (−)-dibromophakellin shows the opposite Cotton effect, despite exhibiting the same absolute configuration.     

First synthesis and absolute configuration of (−)-pyriculariol, a phytotoxin isolated from rice blast fungus, Magnaporthe grisea. Use of microwave irradiation to control Stille coupling reaction products

First total synthesis of (−)-pyriculariol, a phytotoxin isolated from rice blast fungus, Magnaporthe grisea, was achieved to determine the absolute configuration of the natural product to be 5′R,6′S. The key step was Stille coupling reaction using microwave irradiation from −78 °C to control the reaction.     

Synthesis of ent-ambrox® from (−)-nidorellol

Using ozonolysis of the acid-catalyzed cyclized products of (−)-nidorellol and air-autoxidation as the key steps, (+)-ambrox was obtained in 53% overall yield. In the course of our synthesis, we discovered that (−)-nidorellol provided (+)-ambrox instead of the expected product, (−)-ambrox. Thus the absolute configuration of (−)-nidorellol was proved to be trans-(5R^∗,7R^∗,8R^∗,9S^∗,10R^∗)-labda-12,14-diene-7α,8β-diol, which is opposite to that illustrated in a previous report.     

Total syntheses of (+)- and (−)-1,3,4,5-tetragalloylapiitol and revision of absolute configuration of naturally occurring (−)-1,3,4,5-tetragalloylapiitol

The total syntheses of (+)- and (−)-1,3,4,5-tetragalloylapiitol were achieved in seven steps from d- and l-ribose, respectively. By comparing the optical rotations of both enantiomers with those of the natural product, the absolute configuration at C-3 in the naturally occurring 1,3,4,5-tetragalloylapiitol has been revised to R. The absolute configurations at C-3 in the synthetic (+)- and (−)-1,3,4,5-tetragalloylapiitol were further confirmed by the circular dichroism exciton chirality method.     

Absolute configuration assignment made easier by the VCD of coupled oscillating carbonyls: the case of (−)-propanedioic acids, 2-(2,3)-dihydro-3-oxo-1H-isoindol-1-yl)-1,3-dimethyl ester

Depending on their relative orientation, coupled oscillating carbonyl groups provide a VCD spectrum with a characteristic CO bond stretching region showing a strong bisignate VCD feature, which can be readily predicted adopting long available semiempirical methods. The extended coupled oscillator (ECO) formalism has been used to assign the absolute configuration of a recently synthesized chiral 3-substituted isoindolinone. The prediction of (S) configuration for the (−) enantiomer has been confirmed by quantum mechanical calculations.     

Asymmetric synthesis of (−)-chicanine using a highly regioselective intramolecular Mitsunobu reaction and revision of its absolute configuration

First asymmetric synthesis of (−)-chicanine has been accomplished in 14 steps by employing the Evans asymmetric syn-selective aldol reaction, diastereoselective hydroboration and an regioselective, intramolecular Mitsunobu etherification. The absolute configuration of (+)- and (−)-chicanine has been revised to 2R,3S,4R,5R and 2S,3R,4S,5S, respectively, through CD analysis.     

Synthesis and stereochemistry of (−)-rosiridol and (−)-rosiridin

The plant-derived monoterpenoids (−)-rosiridol and (−)-rosiridin can be assembled in an enantioselective manner via DIP-Cl reduction of a ketone precursor obtained by BCl₃-mediated C-C coupling of prenyl stannane and an α,β-unsaturated C₅ aldehyde. On the basis of Mosher analyses, the absolute stereochemistry 4S was assigned to (−)-rosiridol; this was confirmed by X-ray structure analysis of pentaacetylrosiridin. Glucosylation of (4S)-4-acetoxygeraniol proceeds under Koenigs-Knorr conditions in diethyl ether. (−)-Rosiridin was synthesized for the first time.     

Enantioselective total synthesis of (S)-(−)-quinolactacin B

The enantioselective total synthesis of (−)-quinolactacin B (−)-1 was performed in seven steps and 33% overall yield from tryptamine. The synthesis features the use of ruthenium catalytic asymmetric hydrogen reaction to introduce the chirality in dihydro-β-carboline 2. Based on Noyori’s work, the hydrogenation using the (R,R)-TsDPEN-Ru complex produces dihydro-β-carbolines possessing the (S) absolute configuration, the corrected asymmetric center of the natural product. The synthetic quinolactacin B displayed optical rotations that was in accordance with that of the natural product, thereby supporting the (S) configuration for natural quinolactacin B. The final product’s stereochemical assignment is in agreement with that proposed by Nakagawa and co-workers.     

Absolute configuration of bioactive furanogermacrenones from Commiphora erythraea (Ehrenb) Engl. by computational analysis of their chiroptical properties

Absolute configurations (+)-(4S), (+)-(3S,4R), (−)-(2S,4S), and (−)-(1R,2R,4S) were assigned, for the first time, to bioactive furanogermacranes extracted from Commiphora erythraea resin by DFT computational analysis of their ORD curves and ECD spectra. This analysis established that all of these compounds share the same absolute configuration at the methyl-substituted carbon thus allowing us to hypothesize a biosynthetic relationship among these structurally related metabolites.     

Absolute configuration of Tröger bases: an X-ray diffraction and circular dichroism study

Bis-ortho-methyl-bis-meta-bromo Tröger base (TB) 2 and bis-ortho-methyl TB 3 were prepared in enantiopure form. The absolute configuration for (5S,11S)-(−)-2 was determined by X-ray diffraction. The sign of the longest wavelength band in the electronic CD spectrum is negative for both (5S,11S)-(−)-2 and (5S,11S)-(−)-3, as well as for the parent para-methyl TB (5S,11S)-(+)-1, which is in agreement with TD DFT B3LYP/6-31G(d,p) calculations.     

Gold catalysis in stereoselective natural product synthesis: (+)-linalool oxide, (−)-isocyclocapitelline, and (−)-isochrysotricine

A stereoselective synthesis of the tetrahydrofuran-containing natural products (2S,5R)-(+)-linalool oxide (1), (−)-isocyclocapitelline (2), and (−)-isochrysotricine (3) is reported. Key steps are the copper-mediated S_N2′-substitution of propargyl oxiranes 7 and the gold-catalyzed cycloisomerization of dihydroxyallenes 8/17, resulting in a highly efficient center-to-axis-to-center chirality transfer. The enantioselective total synthesis of (−)-isocyclocapitelline (2) and (−)-isochrysotricine (3) allowed the elucidation of the absolute configuration of these β-carboline natural products.     

The first enantiospecific synthesis of (−)-heritol: absolute configuration determination

The first enantiospecific synthesis of (−)-heritol, from naturally occurring (R)-(+)-citronellal and confirmation of its absolute configuration, is described.     

Donnazoles A and B from Axinella donnani sponge: very close derivatives from the postulated intermediate ‘pre-axinellamine’

Two novel dimeric pyrrole-aminoimidazole (PAI) alkaloids (−) donnazoles A-B (1-2) were isolated from the marine sponge Axinella donnani collected off the Mauritius Island. Their structures were elucidated mainly by 2D NMR. Both compounds bear the crucial substituted cyclopentane of ‘pre-axinellamine’, the hypothetical common intermediate of all dimeric PAIs. Additionally, the essential trans-6,7 ring junction of palau′amine’s congeners is already established in 1 and 2. The absolute configurations of 1 and 2 were deduced via NOE correlations in combination with the comparison of their circular dichroism data with the one of (−) sceptrin. The absolute configuration of (−) donnazoles A (1) and B (2) is coherent with the absolute configuration of the known dimeric members of PAI alkaloids.     

Synthesis of (+)-agelasine C. A structural revision

An efficient synthesis of (+)-agelasine C has been achieved from ent-halimic acid. The structure and absolute configuration of the natural product (−)-agelasine C was established and a structure for epi-agelasine C, is proposed.     

Confirmation of the absolute configuration of (−)-aurantioclavine

We confirm our previous assignment of the absolute configuration of (−)-aurantioclavine as 7R by crystallographically characterizing an advanced 3-bromoindole intermediate reported in our previous synthesis. This analysis also provides additional support for our model of enantioinduction in the palladium(II)-catalyzed oxidative kinetic resolution of secondary alcohols.     

Synthesis, resolution and assignment of absolute configuration of trans 3-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (POAC), a cyclic, spin-labelled β-amino acid

Racemic trans 3-(9-fluorenylmethyloxycarbonylamino)-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (Fmoc-POAC-OH), prepared by conventional methods, was resolved upon esterification with (aR)-2,2′-dihydroxy-1,1′-binaphthyl. Separation of the obtained diastereomeric monoesters Fmoc-(±)-trans-POAC-O-(aR)-binaphthol by crystallization/chromatography, and removal of the chiral auxiliary by saponification of the aryl ester function furnished both enantiomers (+)-(3R,4R)-Fmoc-POAC-OH and (−)-(3S,4S)-Fmoc-POAC-OH. The absolute configuration of the asymmetric C³, C⁴ carbons of POAC were assigned from the induced circular dichroism of a flexible biphenyl probe present in the terminally protected dipeptide derivatives Boc-Bip-(+)-POAC-OMe and Boc-Bip-(−)-POAC-OMe (Bip, 2′,1′:1,2;1″,2″:3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid). This assignment was confirmed by X-ray diffraction analysis of the diastereomeric monoester Fmoc-(+)-trans-POAC-O-(aR)-binaphthol, shown to be (aR,3R,4R). Solution synthesis of peptides to the hexamer level, based on the (3R,4R)-POAC enantiomer combined with (1S,2S)-2-aminocyclopentane-1-carboxylic acid, was carried out to examine coupling conditions at both C- and N-termini of the POAC residue, in view of further syntheses and 3D-structural investigations.     

Determination of the absolute structure of albaconol

The concise synthesis of (8aR)-(−)-albaconol (1) from (8aR)-albicanol (2) obtained from the lipase-assisted asymmetric acetylation of rac-2, was achieved in 45% overall yield (eight steps). By comparison of the sign of specific rotation of between synthetic (8aR)-(−)-albaconol (1) and natural (+)-albaconol (1), the absolute structure of natural (+)-1 was determined to be 1R,2R,4aS,8aS configuration.