Synthesis of 2'-O-methoxyethylguanosine using a novel silicon-based protecting group

A short and efficient synthesis of 2'-O-methoxyethylguanosine (8) is described. Central to this strategy is the development of a novel silicon-based protecting group (MDPSCl(2), 2) used to protect the 3',5'-hydroxyl groups of the ribose. Silylation of guanosine with 2 proceeded with excellent regioselectivity and in 79% yield. Alkylation of the 2'-hydroxyl group of 6 proceeded with methoxyethyl bromide and NaHMDS and afforded compound 7 in 85% yield, without any noticeable cleavage of the silyl protecting group and without the need to protect the guanine base moiety. Finally, deprotection of 7 was achieved using TBAF and produced 8 in 97% yield.     

Nα-acyl derivatives of histidine with the di-(2-chloroethyl)amino group

Summary We have obtained new derivatives of histidine containing the di-(2-chloroethyl)amino group; methyl esters of p-di-(2-chloroethyl)aminophenacetyl-, and p-di-(2-chloroethyl)aminophenylbutyrylhistidine and their hydrochlorides. In the same way we prepared p-di(2-chloroethyl)aminophenacetylhistamine.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 917–919, May, 1965 Original article submitted August 5, 1964     

Synthesis and the keto-enol equilibrium of 2-acyl lactams

Condensation of N-substituted lactams with carboxylic acid esters was studied. A wide range of substituted 2-acyl lactams with different ring sizes were synthesized. The structure of 2-acyl lactams (primarily, the ring size) was found to influence the keto-enol tautomerism.     

Synthesis,anti-inflammatory activities and docking studies of amide derivatives of meclofenamic acid

NSAIDs constitute a heterogeneous class of pharmacological agents widely prescribed for the treatment of inflammation, pain and edema, as well as osteoarthritis, rheumatoid arthritis and musculoskeletal disorders. This class of drugs has proved efficacious on account of their analgesic, anti-pyretic and anti-inflammatory activities, but gastrointestinal toxicity exists as the biggest problem associated with their chronic use. Many attempts have been made to structurally modify conventional NSAIDs as selective COX-2 inhibitors based on the old and still prevalent common belief that selective inhibition of COX-2 would provide safer NSAIDs. The present work thus focused on the synthesis of amide derivatives of one of the conventional non-selective NSAID, meclofenamic acid utilizing the one pot procedure involving a selective agent, bis (2-oxo-3-oxazolidinyl) phosphonic chloride. The synthesized compounds were tested for their in vivo inflammatory activity using carrageenan rat paw edema assay, and were subsequently docked on COX-2 PDB code 4COX to have better insights into their mechanism of action. The amide derivative with N-4-methoxybenzyl moiety (TSN4) proved to have anti-inflammatory potential (72.8%) better than meclofenamic acid (56.75%). This compound also docked with the highest dock score among the synthesized compounds and was found to have both hydrogen bonding with Arg120 and Tyr355 and hydrophobic interactions with Val349, Leu352, Ser353, Tyr385, Trp387, Met522, Val523, Ala527 and Ser530. N-4-methoxybenzyl amide derivative (TSN4) followed by benzyl amide derivative (TSN1) of meclofenamic acid were identified as potential anti-inflammatory compounds in both in vivo and in silico studies.     

Synthesis of tryptophans by Lewis acid promoted ring-opening of aziridine-2-carboxylates: optimization of protecting group and Lewis acid

The preparation of tryptophan derivatives through the Lewis acid promoted substitution of aziridine carboxylates with indole was found to be accompanied by a ring-expansion reaction to generate an oxazolidinone byproduct. The ratio of tryptophan to oxazolidinone products can be optimized through a judicious choice of Lewis acid and N-protecting group.     

The comparison of protecting methods to the amino group in 2-Aminomethylphenylacetic acid

2-Aminomethylphenylacetic acid is an important intermediate of ceforanide, and this article compared two different protecting agents for protecting the amino group in 2-aminomethylphenylacetic acid by BOC (Di-tert butyl dicarbonate) or acetacetic ester, and compared the deprotection condition. The yield was higher when BOC was used as protecting agent, but when it was deprotected, it was more difficult than when acetacetic ester was used as protecting agent.     

Intramolecular rearrangement of α-amino acid amide derivatives of 2-aminobenzothiazoles

We have found that α-amino acid amide derivatives of 2-aminobenzothiazoles undergo a time-dependent, thermal rearrangement in which the amine group attacks the 2-position carbon of the thiazole ring to form a 5,5-spiro ring system. This is followed by sulfur leaving and air oxidation to the corresponding symmetrical disulfide. The isolated yields of such products are quite high (>70%) if there is conformational bias to further promote the intramolecular reaction such as for the 2-aminobenzothiazole amides derived from proline or 4-aminopiperidine-4-carboxylic acid. This rearrangement has not been described previously for α-amino acid amide derivatives of 2-aminobenzothiazoles. However, a related reaction involving 2-semicarbazido benzothiazoles has been recently reported.     

芝麻酚酰胺类衍生物的合成及抑菌活性

以芝麻酚为原料,经醚化、硝化、还原和酰胺化合成了9个未见报道的新型芝麻酚酰胺衍生物.其结构经~1H NMR和IR表征,并测定了其抑菌活性.初步生物活性测试结果表明,目标化合物对所有供试病菌均有一定的抑菌活性.4a_4对番茄灰霉病菌、棉花枯萎病菌、小麦赤霉病菌有较好的抑菌活性.4b_1对小麦赤霉病菌的抑制率达到95%;4b_2对番茄灰霉病菌和棉花枯萎病菌的抑制率达到90%以上;4b_3对番茄早疫病菌、番茄灰霉病菌、苹果腐烂病菌和棉花枯萎病菌的抑制率达到90%以上;4b_4对芹菜早疫病菌、番茄灰霉病菌、棉花枯萎病菌和小麦赤霉病菌的抑制率达到90%以上;4c_1对芹菜早疫病菌、番茄早疫病菌、番茄灰霉病菌、苹果腐烂病菌和棉花枯萎病菌的抑制率达到均达到90%以上.     

Synthesis of 2-indolylacetic acid derivatives

2-Indolylacetic acid derivatives were synthesized by condensation of diethyl acetonedicarboxylate with α-substituted arylhydrazines under the conditions of the Fischer reaction, and their transformations were studied.     

Synthesis of amide derivatives of phenophosphazinoic and thiophenophosphazinoic acids

Conclusions Ten new amides of the phenophosphazinoic and thiophenophosphazinoic acids were synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1570–1571, July, 1971.     

Synthesis of fluorinated cyclic s-trans vinylogous acid and amide ester derivatives

A two-step procedure for the preparation of ethyl 4-amino-2-oxo-6-(trifluoromethyl)cyclohex-3-ene-1-carboxylate (enaminone) and methyl 4-hydroxy-2-oxo-6-(trifluoromethyl)cyclohex-3-ene-1-carboxylate (vinylogous acid) has been accomplished, using reactive Michael acceptors under basic condition. In addition, acyclic trifluoromethylated ester derivatives were isolated as competing by-products. The above compounds represent novel synthetically useful trifluoromethyl building blocks.     

1,2-Dimethoxy-4,5-dimethylene: a new protecting group for acyclic amino acid derivatives prepared by Stevens rearrangement

A new protecting group, 1,2-dimethoxy-4,5-dimethylene, for acyclic amino acid derivatives could be introduced by N,N-dialkylation with 1,2-bis(bromomethyl)-4,5-dimethoxybenzene (1) and removed via amine de-alkylation with acyl chlorides. The method can be used with base-induced [2,3] and [1,2] Stevens rearrangement products.     

2-Phenylsulfonylethyl,a new phosphate protecting group: Its application in the synthesis of dodecathymidylic acid.

2-Phenylsulphonylethyl group has been employed for the first time to protect 3′-terminal phosphodiester to the triester level in the synthesis of dodecathymidylic acid using the phosphotriester approach.     

Synthesis of glucuronic acid derivatives via the efficient and selective removal of a C6 methyl group

This investigation is related to the development of a general strategy for the synthesis of certain glucuronic acid derivatives. In particular, we report exceptionally selective conditions for removing the C6 methyl protecting group by potassium hydroxide without affecting the benzoyl protecting groups on the C2, C3 and C4 hydroxyl groups in high yields (95–99%). The present method proves to be efficient and environmentally friendly in terms of short reaction time, high yield and the single product.     

Hydrogen bonding between nucleic acid constituents and amino acid amide group

The formation of hydrogen-bonded complexes between 9-ethyladenine and acetamide in chloroform solution has been studied by infrared spectroscopy. Comparison of the mixed solution spectra with the sum of the spectra of the separate monomers in solution shows that cyclic heterodimers are formed when acetamide binds to adenine base. Information is also obtained about the atomic arrangement of these heterodimers, where acetamide is bound to adenine base predominantly through the pyrimidine ring. Hydrogen bonds of this nature have been also observed for concentrated aqueous solutions of adenosine 5′-monophosphate in the presence of acetamide using Raman spectroscopy.     

2-diphenylmethylsilylethyl group as a new protecting group of internucleotidic phosphates in oligonucleotide synthesis

Internucleotidic phosphates were protected by 2-diphenylmethylsilylethyl which was selectively removed by treatment with tetrabutylammonium fluoride.     

A mild,copper-catalysed amide deprotection strategy: use of tert-butyl as a protecting group

Mild methods for the deprotection of organic substrates are of fundamental importance in synthetic chemistry. A new room temperature method using a catalytic amount of Cu(OTf)₂ is reported. This allows use of the tert-butyl group as an amide protecting group. The methodology is also extended to Boc-deprotection.     

Selective tert-butyl ester deprotection in the presence of acid labile protecting groups with use of ZnBr2

Chemoselective hydrolysis of tert-butyl esters in the presence of other acid-labile groups has been explored by employing alpha-amino esters and ZnBr(2) in DCM. Although N-Boc and N-trityl groups were found to be labile, PhF protected amines were compatible with these Lewis acid deprotection conditions such that a variety of N-(PhF)amino acids were prepared in good yields from their corresponding tert-butyl esters.