A concise route to (+)-lactacystin

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).     

Short syntheses of (+)-ferruginol from (+)-dehydroabietylamine

Short syntheses of bioactive (+)-ferruginol in five or six synthetic steps starting from commercially available (+)-dehydroabietylamine are described. The oxygenated function at C12 was introduced via a Friedel-Crafts acylation of N-phthaloyldehydroabietylamine followed by Baeyer-Villiger oxidation. Then, overall deprotection of functional groups, reductive deamination or biomimetic oxidative deamination, and final Wolff-Kishner reduction provided (+)-ferruginol in 21 and 23% overall yields, respectively.     

A concise synthesis of (+)-pancratistatin using pinitol as a chiral building block

A concise approach toward (+)-Pancratistatin has been achieved via 12 steps from pinitol. An ultrasound assisted arylcerium induced ring opening of cyclic sulfate was employed as a key step.     

Lateral lithiation in terpenes: synthesis of (+)-ferruginol and (+)-sugiol

This paper describes the use of (−)-sclareol in the synthesis of the tricyclic diterpenes of abietane skeleton, such as (+)-ferruginol and (+)-sugiol, using as key step the lateral lithiation of a dinorditerpene derivative.     

A concise route to dihydrobenzo[b]furans: formal total synthesis of (+)-lithospermic acid

A sequence of Sonogashira coupling, Pd(II)-catalyzed carbonylative annulation, and benzofuran reduction (Mg, MeOH, NH(4)Cl) provides a convergent and modular synthetic route to trans-2-aryl-2,3-dihydrobenzo[b]furan-3-carboxylates, which are a structural feature of numerous biologically active natural products. This versatile strategy was applied to the formal total synthesis of the anti-HIV natural product (+)-lithospermic acid.     

A new and concise synthetic route to an enantiopure (+)-conduritol-E derivative from diethyl l-tartrate

(+)-(1R,2R,3S,6S)-3,6-Di-O-methyl conduritol-E was efficiently synthesized in enantiomerically pure form starting from diethyl l-tartrate in 33% total yield using a ring-closing olefin metathesis reaction as one of the key steps.     

Stereoselective construction of a quaternary carbon substituted with multifunctional groups: application to the concise synthesis of (+)-ethosuximide

Synthetically useful β,γ-unsaturated carbonyl compounds having a quaternary carbon at the -position were prepared with high stereoselectivity by the reaction of a dienolate anion derived from ,β-unsaturated imide having a chiral auxiliary and electrophiles (ethyl acetate and allyl iodide as the C₂ and C₃ unit, respectively). This method was applied to a short asymmetric synthesis of (+)-ethosuximide.     

Stereoselective alkylation of tartrate derivatives. A concise route to (+)-O-methylpiscidic acid and natural analogues

The lithium enolate of (2S,3S,5S,6S)-dimethoxy-2,3-dimethyl-1,4-dioxane-5,6-dithiocarboxylate undergoes stereoselective mono- and/or dialkylations to afford two new stereogenic centers. The alkylation products obtained possessed a cis stereochemistry, which was confirmed by the synthesis of natural 4'-O-methylpiscidic acid dimethyl ester .     

A new route to (+)-estrone using a bicyclo[3.2.1]octane chiral building block

A new route to (+)-estrone has been developed starting from the chiral building block having a bicyclo[3.2.1]octane framework based on the inherent stereochemical chemical nature of the chiral building block.     

A practical route to enantiopure, highly functionalized seven-membered carbocycles and tetrahydrofurans: concise synthesis of (+)-nemorensic Acid

Highly diastereoselective thermal [5C+2C] intramolecular pyrone-alkene cycloadditions can be achieved by introducing a homochiral p-tolylsulfinyl group at a suitable position of the alkene. The resulting adducts can be readily desulfinylated to give optically active 8-oxabicyclo[3.2.1]octane derivatives. Interestingly, switching from a sulfinyl to a sulfonimidoyl group allows one to reverse the direction of the diastereofacial selectivity and thereby produces oxa-bridged carbocyclic systems enantiomeric to those obtained from the sulfinyl precursors. Cleavage of the oxa-bridge on the desulfurated adducts yields highly functionalized seven-membered carbocyclic derivatives in enantiopure form. Alternative cleavage of the seven-membered carbocycle provides enantiomerically enriched tetrahydrofurans. We have exploited this reaction pathway for the synthesis of the naturally occurring enantiomer of nemorensic acid.     

A concise route to virginiamycin M2

Modular, fully synthetic routes to structurally complex natural products provide useful avenues to access chemical diversity. Herein we report a concise route to virginiamycin M2, a member of the group A streptogramin class of natural products that inhibits bacterial protein synthesis. Our approach features a longest linear sequence of six steps from 7 simple building blocks, and is the shortest and highest yielding synthesis of any member of the streptogramin class reported to date. We believe this route will enable access to unexplored structural diversity and may serve as a useful tool to improve the therapeutic potential of the streptogramin class of antibiotics.     

A concise route to phytosphingosine from lyxose

Phytosphingosine was synthesized from the commercially available d-2,3-O-isopropylidene-d-lyxofuranose in 28% overall yield by a six-step procedure. This procedure is expedient and flexible for introduction of other lipid moieties on the phytosphingosine structure to make a variety of derivatives that can support the further exploration of their related biological functions.     

A concise route to benzofused macrolactones via ynolides: cycloproparadicicol

A new facile synthesis has been developed for nanomolar Hsp90 inhibitor, cycloproparadicicol (2). Our approach relied on cobalt-complexation promoted RCM, in combination with tandem Diels-Alder/retro-Diels-Alder reactions to assemble the resorcycinylic macrolactone.     

A concise route to a key intermediate in the total syntheses of (+)-tirandamycic acid and (-)-tirandamycin a 2

An efficacious, asymmetric synthesis of the 2,9-dioxabicyclo[3,3,1]nonane 4 has been completed in nine chemical steps from 4,5-dimethylfuraldehyde (8). Since enantiomerically pure 4 has been previously converted in five steps by Ireland into (+)-tirandamycic acid (3) and more recently by Schlessinger into (-)-tirandamycin A (1), this achievement constitutes in a strictly formal sense the total syntheses of these substances. The key step in the synthesis of 4 features the transformation of the enantiomerically pure furfuryl diol 25 into 29 by initial selective oxidation of (the furan ring and subsequent acid-catalyzed bicycloketalization.     

A beta-lactone route to chiral gamma-substituted alpha-amino acids: application to the concise synthesis of (S)-alpha-azidobutyro lactone and a natural amino acid

[reaction: see text] Beta-lactones are useful synthetic intermediates allowing access to a number of functional arrays. In this report, enantiomerically pure 4-trichloromethyl-2-oxetanone is shown to be a versatile amino acid synthon leading to a variety of gamma-substituted alpha-amino acid precursors. The utility of this methodology was demonstrated by the concise synthesis of a protected homoserine equivalent, alpha-azidobutyro lactone, and a naturally occurring alpha-amino acid from the seeds of Blighia unijugata.     

A concise route to indoloazocines via a sequential Ugi-gold-catalyzed intramolecular hydroarylation

A diversity oriented approach for the synthesis of indoloazocines is reported employing an Ugi reaction followed by a gold-catalyzed intramolecular hydroarylation.     

New perspective for natural products synthesis: concise synthesis of (+)-sch 642305 by chiral auxiliary multiuse methodology

The synthesis of (+)-Sch 642305 is an example of chiral auxiliary multiuse methodology, which shows a new perspective for the synthesis of compounds with multiple asymmetric centers. Thus, (+)-Sch 642305 was concisely synthesized from the known compound. Every reaction is stereoselective, and the chiral nonracemic hydrobenzoin worked as chiral auxiliary for desymmetrization of diene, as a template for attaining regio- and stereoselective reactions, as an oxygen source at the C4-position, and as a protecting group of hydroxyl functions. Namely, the chiral auxiliary played a role in every step throughout the synthesis. Furthermore, the synthesis contains a new protocol for obtaining alpha'-alkylated enone compounds.     

A concise route to the right wing of ciguatoxin

A concise route to the HIJKLM-ring fragment 10 of ciguatoxin (CTX) and 51-hydroxyCTX3C was developed in which oxiranyl anion addition and intramolecular carbonyl olefination were utilized as key transformations. The present procedure requires only 23 steps from the I-ring 5, while 35 steps were employed in a previous synthesis of the corresponding right wing 11 of CTX3C. The high efficiency of the present synthesis ensures a supply of 10 for total synthesis and biomedical applications.