Synthesis of glycolipid analogs via highly regioselective macrolactonization catalyzed by lipase

Highly regioselective lipase catalyzed macrolactonization has been used in synthesizing first feedstock based glycolipid analogs. These macrolides containing common disaccharides maltose (4-O-α-d-glucopyranosyl-β-d-glucose) and melibiose (6-O-α-d-galactopyranosyl-β-d-glucose) were synthesized by employing chemoenzymatic methodologies. Maltose and Melibiose were coupled with methyl 15-hydroxy pentadecanoate and then subjected to a highly regioselective macrolactonization at the C-6″ position using Candida antarctica lipase-B to yield the desired products.     

Rapid entry into the cryptophycin core via an acyl-beta-lactam macrolactonization: total synthesis of cryptophycin-24

[see structure]. An efficient, concise approach to the macrolide core of the cryptophycins, potent antimitotic agents, has been achieved. The reaction sequence features a novel macrolactonization utilizing a reactive acyl-beta-lactam intermediate that incorporates the beta-amino acid moiety within the 16-membered macrolide core. This highly modular approach, which allows for multiple alterations throughout the structure, was successfully applied to the total synthesis of cryptophycin-24.     

An acid-catalyzed macrolactonization protocol

[reaction: see text] An efficient macrolactonization protocol devoid of any base was developed derived from the use of vinyl esters in transesterification. Subjecting a hydroxy acid and ethoxyacetylene to 2 mol % [RuCl(2)(p-cymene)](2) in toluene followed by addition of camphorsulfonic acid or inverse addition provided macrolactones in good yields.     

Efficient and versatile stereoselective synthesis of cryptophycins

The cryptophycins are a family of cyclic depsipeptides with four retrosynthetic units A to D which correspond to the respective amino acids and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres by introducing two of them in a catalytic asymmetric dihydroxylation, followed by substrate-controlled diastereoselective reactions. The diol also serves as the epoxide precursor. This approach provides selective access to stereoisomers of unit A (enantiomers, epimers) for structure-activity relationship studies. The unit A derivatives were incorporated into cryptophycin-1, cryptophycin-52 and a novel epimer of cryptophycin-52.     

Synthesis of macrolide antibiotics 21. Retrosynthetic analysis of oleandonolide and macrolactonization of its seco-acid

A retrosynthetic scheme for preparing oleandonolide was examined, and the possibility of macrolactonization of the seco-acid of oleandonolide to a lactone was investigated.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2133–2136, September, 1991.     

Synthesis of nucleoside alpha-thiotriphosphates via an oxathiaphospholane approach

[reaction: see text]. Nucleoside 5'-O-(alpha-thiotriphosphates) were obtained in reactions of the appropriate nucleoside 5'-O-(2-thio-1,3,2-oxathiaphospholanes) with pyrophosphate in the presence of DBU. The presented method allows also for preparation of alpha-seleno congeners and corresponding alpha-modified diphosphates.     

Total Synthesis of Pulchellalactam via an RCM Strategy

Total synthesis of (Z) pulchellalactam, a CD protein tyrosine phosphatase inhibitor, from commercially available methallyl chloride employing ring‐closure metathesis (RCM) as a key step is described.     

Synthesis of vanadium oxide nanotubes via an ultrasonic method

Vanadium oxide nanotubes were synthesized using V₂O₅ powder as the precursor and hexadecylamine as the structure-directing template using a sol-gel reaction method followed by a one-step hydrothermal treatment. The effect of ultrasonics on the formation of nanotubes is reported. The structure and morphology of the nanotubes were investigated by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The inner and outer diameters of the nanotubes varied from 20 to 40 nm and 80 to 100 nm, respectively. The nanotubes measured several micrometers in length.     

A New Total Synthesis of dl-Pumiliotoxin-C via an Indanone

dl-Pumiliotoxin-C (4) was synthesized in a practical manner from trans-4-hexenal (9) . The key step 14 → 15 (Scheme 3) involves an intramolecular Diels-Alder reaction giving mainly the cis-fused indanols 15a , which were converted to the cis-fused ketone 16 . After Beckmann-rearrangement of 16 the octahydroquinolinone 7 was transformed to the lactim-ether 23 . (Scheme 7). Reaction of 23 with propylmagnesium bromide followed by hydrogenation furnished dl- 4 in a highly stereoselective fashion.     

Synthesis of functionalized nitroarylmagnesium halides via an iodine-magnesium exchange

[reaction: see text] Various nitro-substituted aryl and heteroaryl iodides undergo an iodine-magnesium exchange reaction when treated with PhMgCl leading to nitro-containing magnesium organometallics. These Grignard reagents display an excellent stability at temperatures below -40 degrees C and do not undergo electron-transfer reactions. They react as expected with various electrophiles.     

Synthesis of Azocanes from Piperidines via an Azetidinium Intermediate

α-Trifluoromethyl azocanes are accessible from 2-(trifluoropropan-2-ol) piperidines by metal-free ring-expansion involving a bicyclic azetidinium intermediate. The opening of the azetidinium intermediate was achieved by various nucleophiles (amines, alcoholates, carboxylates, phosphonates, halides and pseudo-halides) with an excellent regio- diastereo- and enantioselectivity and in good yields. The relative configuration of the piperidines and azocanes were assigned and the deprotected azocanes offer opportunities for further derivatization.     

Synthesis of functionalized iminolactones via an isocyanide-based three-component reaction

A three-component reaction of the zwitterions generated from isocyanides and dialkyl acetylenedicarboxylate with 1-(4-bromophenyl)-2-thiocyanatoethanone or 1-phenyl-2-thiocyanatoethanone is described. The reaction afforded the corresponding special type of functionalized iminolactone derivatives in good yields at room temperature without using a catalyst.     

Synthesis of an asymmetric fullerene dimer via sequential cycloadditions

A single isomer of a monofunctionalised C₇₀ fullerene is isolated and characterised using variable temperature NMR spectroscopy. Pendant methylene bromide groups allow for further cycloaddition reactions and a C₆₀-C₇₀ asymmetric fullerene dimer is thus prepared.     

Rotaxane Synthesis by an End-Capping Strategy via Swelling Axle-Phenols

A method for rotaxane synthesis by enlargement of the size of the terminal phenol group of the axle component by aromatic bromination has been developed. This method may be regarded as an end-capping strategy involving the swelling of the phenol group at the axle terminal. The advantages of the present strategy include: ready availability of axle components with a variety of swelling precursors, wide product scope (19 examples given including a [3]rotaxane), mild conditions for the swelling process, rich potential for the derivatization of the brominated rotaxanes, and possible release of the axle component by degradative dethreading of the thermally stable brominated rotaxanes under the basic conditions.     

Synthesis of strained cyclic peptides via an aza-Michael-acyl-transfer reaction cascade

A new method is presented to prepare strained lactams. Esterification of the C-terminus of a dipeptide with β-nitrostyrene or quinoline-type auxiliaries is followed by lactam formation by an intramolecular aza-Michael-acyl-transfer reaction cascade. Ultimately, the cyclic tetrapeptide cyclo[Phe-Tyr-Ala-Gly] has been prepared.     

Synthesis of a new siladigermirane via an intramolecular reductive cyclization

Si,Si-diphenyltetramesitylsiladigermirane was synthesized via the intramolecular reductive cyclization of bis(chlorodimesitylgermyl)diphenylsilane using t-BuLi or Rieke magnesium. Addition of water to the siladigermirane resulted in regioselective hydrolysis of the siladigermirane to give 1-(hydroxydiphenylsilyl)-1,1,2,2-tetramesityldigermane.