Biomimetic synthesis of petuniasterone D via the epoxy ester[bond]ortho ester rearrangement

The side chain of the insecticidal steroid petuniasterone D was synthesized by the biomimetic acid-catalyzed epoxy ester[bond]ortho ester rearrangement. In addition to the natural (22R,24R)-configuration of the side chain ortho ester, compounds bearing the epimeric (22R,24S)-, (22S,24R)-, and (22S,24S)- [3.2.1]-bicyclic ortho esters were also produced by stereospecific rearrangement of the corresponding isomeric epoxy esters. Functionalization of the steroid nucleus of the (22R,24R)-ortho ester completed the synthesis of the natural product.     

Facile ring transformation from gluconolactone to cyclitol derivative via spiro sugar ortho ester

[reaction: see text] A short step preparation of cyclitol derivative 8 which is a versatile synthon for the synthesis of valiolamine and its related compounds is described. Key steps in this preparation are a novel enol ether formation from spiro sugar ortho esters with AlMe3 and an intramolecular Aldol condensation of alkyl enol ethers catalyzed by ZnCl2 in THF-H2O. With these reactions, gluconolactone derivative 1 was efficiently converted into 8 in short steps.     

Novel synthesis of a strained para-cyclophane derivative

A [P. Rajakumar, A.M.A. Rasheed, Tetrahedron 61（22） （2005） 5351] para-cyclophane derivative was synthesized via intramolecular esterification of a dipeptide surrogate containing asparagine to form tetrahydropyrimidinone ring. The structures of the product and intermediates were characterized by 1H NMR, 13C NMR and mass spectrum.     

Rearrangement of 4,5α-epoxymorphinan derivatives with carbamoylepoxy rings provide novel oxazatricyclodecane structures

We describe the rearrangement of a carbamoylepoxy 4,5α-epoxymorphinan derivative that provided a novel 4,5α-epoxymorphinan derivative with an oxazatricyclodecane structure via an oxabicyclo[2.2.2]octane intermediate. We proposed the mechanism of the rearrangement reaction based on results observed in different deprotonation conditions. Epimerization occurred during rearrangement under reversible, but not irreversible, deprotonation conditions. The rearrangement product had a novel fundamental structure with moderate affinities for opioid receptors (K_i (μ)=47.7 nM, K_i (δ)=174.6 nM, and K_i (κ)=248.1 nM). Thus, the rearrangement products might have high potency as opioid ligands.     

Nonionic ortho ester surfactants as cleavable emulsifiers

Acid labile surfactants containing an ortho ester link are used as emulsifiers for an aliphatic oil, squalane. The emulsions were made in the presence of a cationic polymer, either polyamine or the corresponding hydrophobically modified polyamine. Spontaneous hydrolysis of the surfactant resulted in emulsions stabilized by polymer together with degradation products from the surfactant. The effect of breakdown of the surfactant on the emulsion was evaluated by means of droplet size measurements and kinetic stability. One linear and one branched nonionic ortho ester surfactant with the same number of oxyethylene units were characterized and used for the purpose. The ortho ester surfactants are complex mixtures of components, ranging from very hydrophilic to very hydrophobic species. The chemical shift of the central methine proton in the ortho ester link is extremely sensitive to the substitution pattern and it was possible to identify by (1)H NMR the components that make up the surfactants, as has been reported earlier. The change in emulsion stability, the change in droplet size and the rate of surfactant hydrolysis were studied at acidic pH at room temperature. Both gas chromatography and (1)H NMR were used in order to monitor the surfactant degradation. The presence of a polymer gave a more sluggish breakdown of the surfactants, probably due to hydrophobic shielding by the polymer. There was a good correlation between increase of droplet size and degree of surfactant decomposition.     

Novel synthesis method of ester free trimethylene carbonate derivatives

Ester free poly(trimethylene carbonate) (PTMC) derivatives show biocompatibility and biodegradability and do not generate any acidic compounds after decomposition. Their syntheses methods are limited however, hampering their material application. Herein, we established a novel synthesis route of ester free trimethylene carbonate (TMC) derivatives. The novel synthesis route was described using six aldehydes and one ketone as starting compounds. The key reaction is the selective deprotection from two protected hydroxyl groups in the cyclic acetal structure by diisobutylaluminium hydride. This novel synthesis route means that it is possible to convert aldehyde group to ether groups in the side chain of TMC. Conventionally, only a substituent derived from a primary alcohol was introduced into the side chain. We therefore succeeded in decreasing the number of reaction steps from five to three, compared with the conventional route. Furthermore, the development of a novel synthesis route enabled the introduction of substituents derived from secondary alcohols, anticipating the creation of further types of ester free TMC derivatives.     

Novel synthesis of 4-chloro-3-hydroxy-2-pyrone by the reaction of acetonide protected 4,5-dihydroxy-2-chloroglycidic ester with magnesium chloride

Treatment of acetonide protected 4,5-dihydroxy-2-chloroglycidic ester with magnesium chloride gave 4-chloro-3-hydroxy-2-pyrone in excellent to good yields.     

新型聚原酸酯共聚物的合成及性能研究

以二聚甘油为原料,经过酯交换及氨基脱保护反应合成了一种两端含氨基的环状原酸酯新单体。该单体与辛二酸/十二烷二酸活性酯缩聚得到两种新的疏水性聚原酸酯共聚物POEAd-1和POEAd-2,其数均分子量分别由凝胶渗透色谱(GPC)测得为1.24×104及1.81×104,分散度(PDI)分别为1.59及1.93。热失重分析法证实POEAd-1和POEAd-2具有较高的热稳定性能,其起始降解温度分别可达198.5℃及202.5℃。溶血试验和MTT细胞毒性试验表明,POEAd-1和POEAd-2均具有良好生物相容性,作为一种潜在的生物医用材料,在药物缓控释领域将具有广阔的应用前景。     

An expeditious synthesis of (+/-)-desepoxy-4,5-didehydromethylenomycin a methyl ester

[formula: see text] A total synthesis of the racemic methyl ester of desepoxy-4,5-didehydromethylenomycin A has been achieved in six steps with an overall yield of 31% starting from diethyl methanephosphonate. The key steps include the Nazarov cyclization of the dienone 7 leading to the alpha-phosphoryl cyclopentenone 8 and the Horner-Wittig reaction of the latter employed for the introduction of the exocyclic methylene moiety.     

Novel synthesis of imidazo[4,5-e][1,4]diazepines

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1140–1141, August, 1990.     

New synthesis of ortho esters of sugars

Summary A new synthesis of ortho esters of sugars has been proposed, starting with 1,2-cis-halogenoses in ethyl acetate medium.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12 p. 2214–2216, December, 1964     

Protein release from poly(ortho ester) extruded rods

Poly(ortho ester) rods containing 15 wt% FITC‐BSA were prepared by extruding an intimate mixture of finely powdered polymer and protein at a temperature where protein activity is retained. After an induction period, linear in vitro release kinetics were obtained with concomitant polymer weight loss.     

The synthesis and reactins of ortho bromophenyllithium

Experimental conditions have now been developed whereby o-bromophenyllithium(II) may be prepared in excellent yields and used as an organometallic intermediate for the synthesis of a variety of ortho bromo substituted phenyl compounds (o-BrC₆H₄X). THe thermal stability, decomposition products and reactions of II wre studied. REactions between II and a variety of substrates, e.g., CO₂, dimethylformamide, fluorinated esters, hexafluorobenzene, and organosilicon chlorides were examined.     

Synthesis of a novel 4,6′-epoxymorphinan derivative and a highly strained novel conjugated ketone

A modification of the 4,5-epoxymorphinan skeleton of naltrexone was carried out to improve the potency and the selectivity of the ligand for an opioid receptor subtype. As one of the modified structures, we newly designed and synthesized a novel 7-membered ring ether derivative, which had an inserted OCH₂ group between the 4- and 6-positions of the morphinan skeleton. The derivative with a 7-membered ring ether, 4,6′-epoxymorphinan, has a more fixed chair form than the 4,5-epoxymorphinan. In addition, we found a new cleavage reaction of the 4,5-epoxy ring in naltrexone, and also obtained a highly strained novel conjugated ketone.     

The reactions of heterocyclic isothiocyanates bearing an ortho ester group with aminoalcohols

Heterocyclic isothiocyanates 1,5,9 , bearing an o-ester group were converted to thiourea derivatives 2a-c, 6a-b , and 10a-b , respectively, using β-aminoalcohols, and to the fused ring systems, e.g., thieno[3,2-d]pyrimidine 4a-b , pyrido[2,3-d]pyrimidine 8 , pteridine 11a , thiazolo[3,2-a]pyrido[2,3-d]pyrimidine 7a-b , and thiazolo[3,2-a]mieno[3,2-d]pyrirnidine 3a-c , derivatives.     

Cascade synthesis of the first imidazo[4,5-e]-thiazolo[2,3-c][1,2,4]triazine derivative

1. Download : Download full-size image

     

Syntheses and polymerization of (meth)acrylates containing spiro ortho ester moieties

Acrylates and methacrylates bearing pendant spiro ortho ester groups ( 3 ) were prepared by the reaction of (meth)acrylic acid with bromomethyl spiro ortho esters ( 2 ) in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). These monomers were copolymerized with styrene (St) at 60°C in the presence of α,α'-azobisisobutyronitrile (AIBN) to give the corresponding copolymers with M?_n 6000-17000 and their compositions were in proportion to the feed ratios. Similarly, the copolymerization of 3 with acrylonitrile (AN) was carried out at 60°C to obtain the corresponding copolymers with the similar compositions to the feed ratios. Two kinds of 3 -St copolymers with different compositions were treated with BF₃OEt₂ in refluxing methylene dichloride affording the crosslinked polymers quantitatively. Slight expansion in volume was observed during the crosslinking.     

二氢(4,5)熏衣草醇的合成

叙述了以易得的异戊醇为原料合成熏衣草醇的一种新型二氢衍生物的方法. 而异戊醇则可以从南中国的糖密发酵制造乙醇的蒸馏残液中得到. 异戊基氯和丙酮的相转移催化缩合以43%的产率得到6-甲基-2-庚酮, 再经甲基化和脱氯化氢导致2,6-二甲基庚烯-2. 该烯烃在氯化锡-二氯甲烷中,与多聚甲醛的Prins反应以41.2%的产率得到二氢(4,5)熏衣草醇. 它似乎是有较淡熏衣草醇香气的类似物.