A concise stereoselective synthesis of pterosin B

Pterosin B is a naturally occurring indanone found in bracken fern (Pteridium aquilinum) that displays a variety of interesting pharmacological properties, but for which few stereoselective syntheses exist. Herein we describe a 7-step stereoselective synthesis of (2R)-pterosin B via 6-bromo-5,7-dimethylindan-1-one whose structure was confirmed by NOE analysis and structure determination by X-ray crystallography. The hydroxyethyl chain was introduced via a Suzuki-Miyaura cross-coupling reaction. The 2-methyl group was introduced stereoselectively by methylation of a SAMP [(S)-1-amino-2-methoxymethyl)pyrrolidine] hydrazone and the chiral auxiliary was removed to produce (2R)-pterosin B. The structure of pterosin B was confirmed by specific rotation and structural determination by X-ray crystallography.     

A concise synthetic approach to dihydrochalcone:First total syntheses of bipinnatone A and B

The first total syntheses of bipinnatone A and B have been achieved starting from commercially available phloroglucinol,p-hydroxybenzaldehyde in ten steps.Key features of the syntheses include Aldol reaction,aryl-alkylation and InCl₃-NaBH₄ selective reduction.     

A short and concise asymmetric synthesis of hamigeran B

The interesting biological properties of the hamigerans wherein hamigeran B is a potent antiviral agent with low cytotoxicity to host cells make these deceptively simple looking structures challenging synthetic targets. A strategy to hamigeran B evolved wherein the three contiguous stereocenters are established ultimately from a Pd catalyzed asymmetric allylic alkylation (AAA). The latter involves an asymmetric allylation of a non-stabilized ketone enolate in 77 % yield and 93 % ee. By using this process, (S)-5-allyl-2-isopropyl-5-methyl-1-trifluoromethanesulfonyloxycyclopentene becomes available in four steps from 2-methylcyclopentanone. Introduction of the aryl unit by cross-coupling proceeded intermolecularly but failed intramolecularly. On the other hand, reductive removal of the triflate permitted a Heck reaction to effect intramolecular introduction of the aryl ring. The unusual conformational properties of this molecular architecture are revealed by the regioselectivity of the beta-hydrogen elimination in the Heck reaction and the diastereoselectivity of the reduction establishing the stereochemistry of the carbon bearing the isopropyl group. The successful route consists of 15 steps from 2-methylcyclopentanone and dimethylorcinol illustrating the efficiency of the route based upon the Pd AAA.     

Rapid synthesis of indole cis-enamides via hydroamidation of indolic alkynes

The synthesis of indolic cis-enamides using a ruthenium-mediated hydroamidation of indole alkynes with primary oxalamides or α-keto amides is reported. Using this method the total synthesis of igzamide and Z-coscinamides A and B has been achieved.     

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.     

Solid-phase synthesis of cyclic hexapeptides wollamides A,B and desotamide B

Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cocktail of trifluoroacetic acid/triisopropylsilane/dichloromethane afforded the desired cyclic hexapeptides, which were characterized by ¹H, ¹³C NMR, and HRMS. Subsequent investigation of macrocyclization parameters such as terminal residues, coupling reagents, and cyclization concentration revealed the optimized conditions for the synthesis of this class of cyclic hexapeptides.     

Total synthesis of (+)-crocacin A

Total synthesis of the potent antifungal and cytotoxic agent (+)-crocacin A is described. The crucial (Z)-5,6-enoic amide moiety in this molecule was built by stereoselective partial reduction of a skipped diyne precursor. The diene, thus obtained, was transformed into a silyl epoxide that was regioselectively opened with an azide ion to furnish an α-azido-β-hydroxyalkylsilane intermediate. Peterson elimination of this β-hydroxysilane component in the final step resulted in the formation of the (Z)-8,9-enamide moiety of the molecule leading to a successful completion of its total synthesis.     

A concise total synthesis of lyngbic acid,hermitamides A and B

A concise total syntheses of lyngbic acid, hermitamides A and B have been accomplished in a highly enantioselective manner involving CBS asymmetric reduction, hydroboration, and stereospecific Julia–Lythgoe olefination.     

First total synthesis of rhuscholide A,glabralide B and denudalide

The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho-alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide.     

Versicolactones A and B: total synthesis and structure revision

To further determine absolute configurations of versicolactones A and B, total synthesis of versicolactones A and B and their six stereoisomers were reported in this Letter. The ¹H and ¹³C NMR spectra of the synthetic erythro-stereoisomers matched perfectly with those of the natural products. Combined with the comparison of the specific rotations, the absolute configuration of versicolactones A and B were revised as (4Z,6R,7S)- and (4E,6R,7S)- from the corresponding (4Z,6R,7R)- and (4E,6R,7R)-6,7-dihydroxyocta-2,4-dien-4-lactone, respectively.     

First total synthesis and reassignment of absolute configuration of diosniponol A and B

Enantioselective first total synthesis of diosniponol A and B has been achieved starting from commercially available vanillin. Wittig reaction, Keck allylation, and Prins cyclization reactions are the key steps involved in the target synthesis.     

Total synthesis of emericellamides A and B

The total synthesis of emericellamides A and B is reported. A convergent, flexible strategy employing peptide chemistry, asymmetric alkylations, and culminating in macrolactamization is described. The previously reported structure of both compounds is confirmed.     

A concise synthesis of d,l-brevianamide B via a biomimetically-inspired IMDA construction

A concise synthesis of brevianamide B has been accomplished using a biomimetically-inspired intramolecular Diels-Alder reaction to diastereoselectively form the characteristic bicyclo[2.2.2]diazooctane core.     

A concise synthesis of the functionalized [5-7-6] tricyclic skeleton of guanacastepene A

The six membered ring of guanacastepene A was constructed by a Diels-Alder reaction of 1,1,4-trisubstituted diene to set up the correct relative stereochemistry at the C8 quaternary center and the remote C5 stereocenter. In 10 efficient steps from the Diels-Alder adduct 9, the desired highly functionalized [5-7-6] tricyclic skeleton 2 was synthesized. Key steps involve trimethylsilyl chloride (TMSCl) assisted Michael addition to form enol ether and the usage of the enol ether in the following intramolecular Mukaiyama aldol reaction to form the middle seven membered ring of guanacastepene A.     

A concise synthesis of chilenine via a sequential reaction process

A new short synthesis of chilenine has been achieved in two steps. The precursor amide was readily prepared by the condensation of the corresponding amine and acid. Treatment of the amide with oxalyl chloride in the presence of AlCl₃ at room temperature afforded the desired product chilenine through sequential Friedel-Crafts acylation, amide cyclization to imide, and intramolecular Friedel-Crafts type reaction. The synthesis suggests a new potential of oxalyl chloride for a two-carbon synthon.     

A concise and stereoselective total synthesis of L-783,290

A stereoselective total synthesis of L-783,290 has been achieved involving Alder–Rickert reaction, ring closing metathesis, and chemoselective oxidation as key steps. This approach has successfully demonstrated a linear sequence of reactions, which are highly stereoselective for the construction of the resorcylic acid unit.     

A concise synthesis of topsentin A and nortopsentins B and D

[reaction: see text] A concise synthesis of topsentin A (R(1) = R(2) = H) and nortopsentins B (R(1) = Br, R(2) = H) and D (R(1) = R(2) = H) is described from oxotryptamine 5 via reduction of acyl cyanide 4. Regiospecific bromination of 3-cyanoindole afforded 6-bromo-3-cyanoindole (10) as the major product.     

A two-step biomimetic synthesis of antimalarial robustadials A and B

The antimalarial robustadials A and B have been synthesized in two steps starting from commercially available phloroglucinol comprising a key biomimetic three-component reaction that involves in situ generation of an o-quinone methide via Knoevenagel condensation and subsequent Diels-Alder cycloaddition with (−)-β-pinene.