Organocatalytic enantioselective synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide

The organocatalytic synthesis of quinolizidine alkaloids (+)-myrtine, (−)-lupinine, and (+)-epiepiquinamide is described. It involved, as the key step, an enantioselective intramolecular aza-Michael reaction (IMAMR) catalyzed by Jørgensen catalyst I, affording the common precursor with high enantioselectivity. This compound was subsequently transformed into the three alkaloids in a highly diastereoselective manner.     

Total synthesis of (+)-epiepoformin and (−)-phyllostine

An efficient asymmetric total synthesis of naturally occurring cyclohexeneoxides, (+)-epiepoformin and (−)-phyllostine has been achieved using the chiral building block available from the base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone. Since (−)-theobroxide was derived from the same precursor of (+)-epiepoformin, the formal total synthesis of (−)-theobroxide has also been achieved.     

Stereoselective synthesis of tetrahydroisoquinoline alkaloids: (−)-trolline, (+)-crispin A, (+)-oleracein E

Tetrahydroisoquinoline alkaloids, (S)-(−)-trolline, (R)-(+)-crispin A, and (R)-(+)-oleracein E, have been synthesized stereoselectively from the both enantiomers of common intermediate (S)-4 and (R)-4. The key step in the synthesis include a stereoselective Bi(OTf)₃-catalyzed intramolecular 1,3-chirality transfer reaction of chiral non-racemic amino allylic alcohols (S)-6 and (R)-6 to construct both enantiomers of (E)-1-propenyl tetrahydroisoquinoline 4.     

Total synthesis of (−)-clavosolide A

The total synthesis of (−)-clavosolide A is achieved employing a radical-mediated route to build the substituted tetrahydropyran unit, a Yamaguchi reaction to construct the diolide aglycon and the Schmidt method for the final glycosidation step.     

Enantioselective, chemoenzymatic synthesis, and absolute configuration of the antioxidant (−)-gloeosporiol

The natural antioxidant (−)-gloeosporiol, isolated as a peracetylated derivative from a culture of the fungus Colletotrichum gloeosporioides, has been enantioselectively prepared from 3,4-dihydroxybenzaldehyde by means of a chemoenzymatic synthesis. The key intermediate was obtained by resolution with a lipase from Pseudomonas cepacia. Its stereochemistry, initially assigned as R, according to the Kazlaukas empirical rule for secondary alcohols, was independently confirmed by NMR and chirooptic methods. This, in turn, allowed the assignment of compound (−)-1 as (−)-(2S,3R,4R)-2-(3′,4′dihydroxyphenyl)tetrahydrofuran-3,4-diol.     

Total synthesis of (−)-radicamine B

The synthesis of a chiral cyclic nitrone with l-arabino configuration and its application in the total synthesis of radicamine B is reported. An agreement in the spectral data with natural radicamine B but specific rotation with an opposite sign warranted a revision of the absolute configuration of radicamine B.     

Total synthesis of (−)-incarvilline

An enantioselective synthesis of (−)-incarvilline is presented, employing a three-component coupling reaction and an intramolecular enone-olefin [2+2] photocycloaddition followed by a SmI₂-induced cyclobutane ring-opening reaction.     

Total synthesis of racemic,natural (+) and unnatural (−) scorzocreticin

The first total synthesis of racemic scorzocreticin and its pure enantiomers is described from readily available 3,5-dihydroxybenzoic acid. The key steps include Wittig olefination, asymmetric Me-CBS (Corey–Bakshi–Shibata) oxazaborolidine reduction, and improved Pd-catalyzed intramolecular lactonization reactions. Both the (S)-natural and (R)-unnatural enantiomers of scorzocreticin have been synthesized in excellent enantioselectivities (>99% and 99% ee, respectively). In addition, 1,10-phenanthroline, a bidentate N-ligand was employed in palladium-catalyzed intramolecular carbonylation/lactonization reaction for the construction of 3,4-dihydroisocoumarin ring.     

Synthesis of marine bisindole alkaloids, hamacanthins A and B through intramolecular transamidation-cyclization

The total syntheses of the marine bisindole alkaloids, hamacanthins were achieved by a novel transamidation-cyclization of N-(2-aminoethyl)-2-oxoethanamides to 3,5- and 3,6-disubstituted piperazinones.     

Asymmetric synthesis of quinolizidine alkaloids (−)-lasubine I, (−)-lasubine II and (+)-subcosine II

The enantioselective synthesis of (−)-lasubine I 1 and the first asymmetric synthesis of (−)-lasubine II 2 and (+)-subcosine II 3 is described. The key step is the intramolecular cyclization of N-acyliminium ion 4 which is derived from (S)-aminoester 6.     

Meloslines A and B,two novel indole alkaloids from Alstonia scholaris

An unprecedented indole alkaloid melosline A (1), with 6/5/6/6 tetracyclic ring skeleton, together with a new alkaloid melosline B (2) and one known compound (3) were isolated from the leaves and twigs of Alstonia scholaris. The new structures were elucidated by comprehensive spectroscopic analysis. The absolute configuration of compound 1 was confirmed by comparison of experimental data with calculated electronic circular dichroism (ECD). Compound 1 exhibited moderate cytotoxicity against MCF-7 cancer cell lines.     

Total synthesis of the marine sponge metabolites (+)-rottnestol, (+)-raspailol A and (+)-raspailol B

The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.     

Total synthesis of (−)-diospongin A and (+)-cryptofolione via asymmetric aldol reaction

Stereoselective synthesis of two distinctive pyranone skeletons diospongin A and cryptofolione has been described based on an asymmetric aldol reaction starting from Chan’s diene. The synthetic strategy involves the enantioselective Mukaiyama aldol, diastereoselective reduction of δ-hydroxy-β-keto ester, a tandem sequence of deprotection, and intramolecular oxa-Michael reaction to obtain diospongin A and an asymmetric allylation and lactone formation using ring-closing metathesis reaction to obtain cryptofolione.     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.     

A short synthesis of (+) and (−)-falcarinol

A short, practical synthesis of the bis-acetylenic natural product falcarinol 1 is reported. This method relies on the alternate functionalisation of bis-trimethylsilylbutadiyne 10. This may be achieved in one-pot, however, better yields were obtained more conventionally. Lipase mediated enzymatic kinetic resolution of the racemic adduct in an organic solvent afforded (+)-1 in 97% enantiomeric excess. The analogous process performed with racemic 3-acetoxy falcarinol 11 under aqueous conditions gave (−)-1. Oxidation of 1 with Dess-Martin periodinane gave falcarinone 2.     

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.     

First enantiospecific synthesis of marine nor-sesquiterpene (+)-austrodoral from (−)-sclareol

A short and efficient synthesis of the rearranged nor-sesquiterpenes (+)-austrodoral (1) and (+)-austrodoric acid (2), recently isolated from the Antarctic marine mollusk Austrodoris kerguelenensis, from diterpene (−)-sclareol (4) is reported. The key step of the sequence is the pinacol rearrangement of the drimanetriol 11.     

A versatile synthesis of (+)-deoxoprosopinine and (−)-deoxoprosophylline

An efficient synthesis of (+)-deoxoprosopinine and (−)-deoxoprosophylline was achieved from N-benzyl-N-Boc serine derivatives (7) and (7′).     

Total synthesis of (−)-centrolobine

Stereoselective synthesis of (−)-centrolobine, an anti-Leishmania agent, was accomplished via an intramolecular Barbier-type reaction of iodo-ester with n- or t-butyllithium followed by Lewis acid-promoted Et₃SiH reduction of the resulting hemiacetal.     

Total synthesis of (−)-muricatacin

A total synthesis of (−)-muricatacin has been achieved using a commercially available starting material and our furan approach to oxacyclic systems, the proven scope of which is thus broadened.