Synthesis of C-17-functionalized spongiane diterpenes: diastereoselective synthesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1, and (-)-aplyroseol-14

The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyldendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial (-)-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)-acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unprecedented delta-lactone-based structure for spongiane-type diterpenoids. A theoretical study including a series of ab initio calculations for the mechanism involved in the conversion of ester 22 into natural product 2 has also been carried out.     

Maillard Polymers Derived from D-Glucose-1 and -6-14C,Glycine-1 and -2-14C,and C-1-, and Methyl-14C Methionine

Maillard polymers were prepared from D-glucose-1 and -6-14C, glycine-1 and -2-¹⁴C, as well as C-1 and methyl-¹⁴C methionine, and the activities of the isolated polymers measured as a function of time. In both cases, C-1 of the amino acids were incorporated at the lowest levels, with D-glucose carbon atoms at the highest levels. The data support the conclusions that carbon dioxide, produced during the Maillard reaction, arises from C-1 of the amino acids, but also suggests that other carbons of the amino acids may contribute as well.     

Synthesis of [1-14C]-labeled mandelic acid under microwave condition

Summary We report here a facile synthesis of [1-¹⁴C]-mandelic acid. Benzyl bromide on cyanation with K¹⁴CN followed by acid hydrolysis in a microwave oven gave [1-¹⁴C] phenylacetic acid. The latter on a-bromination followed by hydrolysis under microwave irradiation for 2 minutes furnished the title compound.     

Syntheses of (±)-17α- and (±)-17β-hydroxytacamonine; determination of configuration at C-17

Both (±)-17α-hydroxytacamonine (3) and its 17β-isomer (4) were synthesized in two steps (one-pot) from aldehyde mixture 5/6 via the cyanohydrin reaction. NMR spectral characterization of isomer 3 revealed it to be unidentical with natural 17-hydroxytacamonine, whereas spectral data of isomer 4 were in agreement with those published for the natural isomer. The configuration at C-17 was confirmed by NOE difference spectroscopy.     

Synthesis of C-3 side-chain carboxylic acid cannabinoid derivatives

Based upon the structural similarities of cannabinoid derivatives which inhibit the biosynthesis of prostaglandins with those of the potent inhibitor, indomethacin, several cannabinoid derivatives possessing C-3 side chain carboxylic acid functionalities were prepared.     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

17O and 14N spectroscopy of 17O-labeled nucleic acid bases

Oxygen-17 and nitrogen-14 nuclear magnetic resonance techniques have been utilized in studying liquid-state hydrogen bonding interactions between nucleic acid bases and between the bases and solvent. The bases uracil and thymine have been labeled with ¹⁷O at positions 2 and 4, cytosine at position 2 and thymine riboside at position 4. The ¹⁷O chemical shift was found to be a sensitive structural probe and to provide information concerning the resonance forms that contribute to the total wave function. The chemical shift of the oxygen of thymine and uracil at position 2 was detected at a higher field than that of oxygen at position 4, presumably owing to an increased contribution of single bonded-oxygen valence bond structures at position 2. The ¹⁷O and ¹⁴N chemical shifts of cytosine were found to be strongly pH dependent, and the results have been interpreted in terms of predominant cytosine resonance structures contributing to the aqueous cation and anion. The ¹⁷O line width of cytosine in aqueous solution indicates the presence of hydrogen bonded dimers between neutral and cationic forms.     

Preparation of O-1∼C-6 and O-7∼C-14 fragments of colletodiol

(5S,2E)-5-Tetrahydropyranyloxy-2-hexenoic acid and p-toluenesulfonylethyl (4R,5R,7R,2E)-7-hydroxy-4,5-dimethylmethylenedioxy-2-octenoate were prepared from ethyl acetoacetate and D-glucose, respectively.     

14β-hxdroxy steroids - III. Synthesis of digoxigenin from deoxycholic acid

A new synthetic approach to cardenolides is discussed which employs singlet oxygen addition to dienol ethers and an intramolecular Prins reaction.     

Versatile routes to C-2- and C-6-functionalized glucose derivatives of iminodiacetic acid

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-alpha-beta-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-alpha-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a-c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of alpha and beta anomers.     

Absolute stereochemistry of amphidinolide C: synthesis of C-1-C-10 and C-17-C-29 segments

Two of each diastereomers of the C-1-C-10 and C-17-C-29 segments of amphidinolide C (1) were synthesized. Comparing the ¹H NMR chemical shifts of its MTPA esters with those of linear methyl ester of 1, the absolute configurations at C-7, C-8, C-20, C-23, and C-24 in amphidinolide C (1) were confirmed to be all R.     

Carbon-14 kinetic isotope effect in the decarbonylation of lactic acid[1-14C]

The carbon-14 kinetic isotope effect for the decarbonylation of lactic acid[1-¹⁴C] in sulfuric acid has been measured in the temperature interval of 20–90°C. The experimental values of (k_12C/k_14C) are compared with the theoretical¹⁴C kinetic isotope effect calculated assuming that one carbon-oxygen stretching vibration is lost in the rate-determining step. The discrepancy between experimentally observed temperature dependence of the¹⁴C kinetic isotope effect and the theoretical one is explained by the possible side reactions which change the apparent degrees of decarbonylation and isotopic composition of CH₃CHOHCOOH[1-¹⁴C] used in experiments aiming at the determination of carbon-14 kinetic isotope effect in the decarbonylation process itself.