Step-economic synthesis of (±)-debromoflustramine A using indole C3 activation strategy

A concise and practical strategy to obtain C3 reverse-prenylated pyrrolidinoindoline scaffold has been executed in 28.8% overall yield. The key conjugative step involved a Booker-Milburn-Feudoloff reaction involving an NCS-mediated activation of indole, followed by coupling to C₅ dimethylallylalcohol. This linchpin step proceeded in 74% yield. The overall sequence proceeded in five steps from commercially available N-methyltryptamine with a single protection-deprotection operation and a single redox manipulation. Mechanistic insights of NCS activation, and an ensuing rearrangement of the isoprene unit were gained by rationally varying the C3 substituent.     

Stereoselective total syntheses of (+)-exo- and (−)-exo-brevicomins, (+)-endo- and (−)-endo-brevicomins, (+)- and (−)-cardiobutanolides, (+)-goniofufurone

Stereoselective total syntheses of aggregation pheromones (+)-exo-brevicomin (9a), (−)-exo-brevicomin (9b), (+)-endo-brevicomin (9c), (−)-endo-brevicomin (9d) and styryllactones (+)-cardiobutanolide (14a), (−)-cardiobutanolide (14b), and (+)-goniofufurone (19a) were achieved in good yields from enantiomerically pure highly functionalized furanoid glycal building blocks (1a-d) involving similar synthetic strategies, thus making these furanoid glycals highly useful building blocks in diversity-oriented synthesis (DOS).     

A concise diastereoselective approach to (+)-dexoxadrol, (−)-epi-dexoxadrol, (−)-conhydrine and (+)-lentiginosine from (−)-pipecolinic acid

A new diastereoselective pathway for the total synthesis of (+)-dexoxadrol, first asymmetric synthesis of (−)-epi-dexoxadrol and formal synthesis of conhydrine and (+)-lentiginosine is presented using commercially available (−)-pipecolinic acid. The key reactions utilized are Sharpless asymmetric dihydroxylation and Wittig reaction. The paper further describes the study of effect of protecting groups on dihydroxylation of a terminal olefin in piperidine ring system.     

Total synthesis of marine bisindole alkaloids, (+)-hamacanthins A, B and (−)-antipode of cis-dihydrohamacanthin B

The total synthesis of the marine bisindole alkaloids, (+)-hamacanthins A (2a) and B (2b), and (−)-antipode of cis-dihydrohamacanthin B (2e) was achieved by transamidation-cyclization of N-(2-aminoethyl)-2-oxoethanamide 18 derived from (S)-indolylglycinol 10.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Stereoselective synthesis of (−)-malyngolide, (+)-malyngolide and (+)-tanikolide using ring-closing metathesis

The stereoselective syntheses of the naturally occurring δ-lactones (+)-tanikolide and (−)-malyngolide as well as of the unnatural (+)-enantiomer of the latter are described. Key steps in each of these syntheses were stereoselective additions of organometallic reagents to α-oxygenated ketones and olefin ring-closing metatheses.     

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.     

Stereoselective synthesis of (−)- and (+)-pentenomycins using RCM

An efficient synthesis of enantiopure (−)- and (+)-pentenomycins are described by reductive iodo elimination and ring-closing metathesis (RCM), as the key steps. The first synthesis of the unnatural (+)-isomer is described.     

A short enantioselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation

An efficient enantioselective synthesis of (−)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.     

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.     

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′).     

Novel synthetic strategy toward abietane and podocarpane-type diterpenes from (−)-sclareol: synthesis of the antitumor (+)-7-deoxynimbidiol

A new route to abietane and podocarpane-type terpenoids from labdane diterpenes is reported. The key step is the transformation of β-ketoester 9 into the corresponding O-acetylsalicylate ester 18, via a manganese(III)-based oxidative free-radical cyclization carried out in Ac₂O. Utilizing this, the synthesis of the antitumor (+)-7-deoxynimbidiol (5) from (−)-sclareol (11) has been achieved. (+)-Nimbidiol (6) and the natural terpenoid 20 have also been synthesized.     

Stereoselective synthesis of (−)-cytoxazone and (+)-epi-cytoxazone

Optically pure (−)-cytoxazone was synthesized, starting from methyl p-methoxycinnamate, in six steps and in 31% overall yield. The required anti-aminoalcohol configuration was established by combining Sharpless asymmetric aminohydroxylation with the configurational inversion of the intermediate amidoalcohol via an oxazoline. The synthesis of (+)-epi-cytoxazone is also described.     

The syntheses of rac-inthomycin A, (+)-inthomycin B and (+)-inthomycin C using a unified synthetic approach

The Stille coupling between a common oxazole vinyl iodide and stereodefined stannyl-diene units is described as the cornerstone of a unified synthetic route to the inthomycin family of bioactive Streptomyces metabolites. This procedure has been utilised to prepare (+)-inthomycin B and (+)-inthomycin C for the first time; in these examples the stereogenic centre was introduced using the Kiyooka ketene acetal/amino acid-derived oxazaborolidinone variant of the Mukaiyama aldol reaction. In addition, a convenient preparation of rac-inthomycin A is described based on the same strategy.     

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.     

New asymmetric strategy for the total synthesis of naturally occurring (+)-alexine and (−)-7-epi-alexine

A novel and highly convenient process is described for the asymmetric synthesis of polyhydroxylated pyrrolizidine alkaloids, (+)-alexine [(1R,2R,3R,7S,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine] and (−)-7-epi-alexine [(1R,2R,3R,7R,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], as the potent glycosidase inhibitors by featuring the efficient and stereodefined elaboration of the functionalized pyrrolidine derivatives, which were, in turn, prepared via stereoselective manipulation of the homochiral allyl alcohol precursors derived from l-xylose.     

Enantioselective total syntheses of (+)- and (−)-ottelione A and (+)- and (−)-ottelione B. Absolute configuration of the novel, biologically active natural products

Following our recent total synthesis of the biologically potent natural products otteliones A and B in racemic form, we have now accomplished the total synthesis of both the enantiomers of otteliones A and B through an enantiodivergent strategy emanating from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone. These endeavors have led to the elucidation of the absolute configuration of naturally occurring otteliones A and B.     

Indole diterpene synthetic studies: development of a second-generation synthetic strategy for (+)-nodulisporic acids A and B

A second-generation strategy for construction of (+)-nodulisporic acids A and B based on the development of a new, effective modular indole synthesis exploiting a sequential Stille cross-coupling/Buchwald-Hartwig union/cyclization tactic is disclosed. This strategy evolved due to the considerable acid instability of the C(24) hydroxyl group observed in several advanced intermediates during our first-generation approach.     

Synthesis of (+)- and (−)-isocarvone

The first synthesis of 5-isopropenyl-3-methyl-cyclohex-2-enone, (isocarvone) (2), in enantiomerically pure form is reported. Both enantiomers of 2 can be produced by manipulation of carboxylic acid 5, which is available from R-(−)-carvone (1). These materials provide new chiral building blocks that could be used in total synthesis of natural products and related optically active compounds.     

A synthesis of (−)-ebelactones A and B

A synthesis of the β-lactone esterase inhibitors (−)-ebelactones A and B is described. The synthesis features the use of a Hoppe homoaldol reaction and a Cu(I)-mediated 1,2-metallate rearrangement of a metallated enol carbamate as key fragment linkage reactions.