Synthesis of .BETA.-(sec-Amino)alanines.

Abe, Nobuhiro; Fujisaki, Fumiko; Sumoto, Kunihiro

doi:10.1248/cpb.46.142

Cited by 15 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficient synthesis of starting material 6 and related compounds has already been reported. 3) To begin, we attempted the procedure via amidation of the carboxylic acid functionality. Thus treatment of 6 with methanolic hydrogen chloride gave the corresponding amino acid methyl ester 7 in excellent yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of N-[2-(1-Piperidinyl)ethyl] benzamides.

Fujisaki

Abe

Sumoto

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

In the course of our studies on the chemistry of enaminoketones, 1) we synthesized some enamino-ketone Mannich base derivatives depicted by the general formula 1 (Chart 1), and found that most had strong opioid analgesic activity. 2)Among the derivatives synthesized, compound 1a or 1b showed higher analgesic acitivity than that of morphine, and both compounds had various pharmacological activities such as sedative, antitussive, or anticonvulsant activities. These results suggested that 1a or 1b can interact with a variety of receptors in the central nervous system. On the basis of those studies, we attempted the chemical modification of the prototype compound 1 as shown in Chart 2. Thus the alicyclic moiety (part A enclosed in the dotted lines in 1) was removed and the vinylogous amide moiety was divided into two amide moieties (parts B and C in structure 2), leading to the malonodiamide Mannich base 2. However, the synthesized compounds 2 were unstable. Therefore we planned to synthesize the Mannich base 3 in which the anilide moiety (part C in 2) was replaced with a benzamide group. This molecule 3 bears a marked structural resemblance to some dopamine antagonists. In this paper, we report the synthesis of novel benzamide derivatives (4 and 5 in Chart 3) with the general structure 3. Results and DiscussionFor the preparation of the target compounds 4 and 5 starting from b-piperidinoalanine 6, two rational synthetic pathways via amidation of this amino acid are possible. The efficient synthesis of starting material 6 and related compounds has already been reported.3) To begin, we attempted the procedure via amidation of the carboxylic acid functionality. Thus treatment of 6 with methanolic hydrogen chloride gave the corresponding amino acid methyl ester 7 in excellent yield. The ester dihydrochloride 7 was reacted with methylamine and pyrrolidine to give corresponding amides 8 and 9 (87 and 72% yield, respectively), which were used in next step without further purification. Treatment of compound 8 with carboxylic acids in the presence of dicyclohexylcarbodiimide (DCC) gave the desired benzamide derivative 4. In a similar manner, the reaction of 9 with carboxylic acids afforded corresponding benzamide derivatives 5a-d. Since no reaction of 7 with piperidine occurred, 4) alternative amidation of the target compound 5e was investigated and we found that a method via mixed anhydride was efficient. Thus the reaction of 6 with benzoyl chloride under Schotten-Baumann reaction conditions gave N-[(1-carboxy)-2-(1-piperidinyl)-ethyl]benzamide 10 in good yield. The reactant of 10 with pivaloyl chloride, giving a corresponding mixed anhydride, was allowed to react with piperidine to provide the desired 5e in 50% yield. Using this procedure, compound 5a was also obtained from 10 and pyrrolidine in 63% yield (see Chart 3). This method via mixed anhydride was also applicable for the preparation of 4 and 5b-d and provides a new synthetic procedure for this class of compounds. The results are summarized in Table 1. 5)The molecu...

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of N-[2-(1-Piperidinyl)ethyl] benzamides.

Fujisaki

Abe

Sumoto

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

show abstract

“…The preparation of racemic b-aminoalanines as starting materials has already been described in our previous paper. [1][2][3][4] The following abbreviations in the brackets were used for the cyclohexane ring (Cyhx), the piperidine ring (Ppd), and for the oxazolidinone ring (Oxaz), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

See 1 more Smart Citation

Preferential Intramolecular Ring Closure of Aminoalcohols with Diethyl Carbonate to Oxazolidinones

Fujisaki

Oishi

Sumoto

2007

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

In connection with our interest in the chemistry of baminoalanines, [1][2][3][4] we have reported the synthetic application of these materials as a synthon for the preparation of a 5-membered oxazolidinone ring system.2) Some of the oxazolidinone derivatives have attracted much attention not only as a synthetic target but also because of the importance of the related compounds in the biological activities. 5,6) This paper deals with the relative rates of ring closure by cyclization with diethyl carbonate (EtO) 2 CO from aminoalcohols as starting material. We report here two typical experimental results for the cyclization that has two possibilities as a function of the ring intramolecular cyclization by (EtO) 2 CO.1 Results and DiscussionsThe objective of this report is to explore the orientation of ring closure of aminoalcohol by (EtO) 2 CO. The compounds (1 7) and 6 8)) are selected as the starting aminoalcohols, which have two hydroxy groups and a basic secondary amine in the molecules, so that the cyclization of these compounds employing (EtO) 2 CO can lead to the corresponding heterocycles (e.g. compounds 2 and 3, respectively, in the case of aminoalcohol 1).Since the experiment using compound 1 under similar reaction conditions reported previously 2) resulted in a quite complex reaction mixture by TLC analysis, it is not used to determine conditions suitable for cyclization of this aminoalcohol (1). Then, we tried the cyclization of (1) under the conditions of this aminoalcohol (1) , 2b). Because a diastereomeric mixture of aminoalcohol (1) (cis : transϭca. 3/1) was used as the starting material (see Experimental), the 5-membered ring products (oxazolidinones) may generate the products 2 as a mixture of four diastereoisomers theoretically.We were able to isolate two cis-isomers (2a, b, a or bstereoisomers, respectively), and our repeated trials for separation of two pure trans-isomers were unsuccessful. However, NMR spectroscopic analysis showed the isolated sample 2c was a mixture of two stereoisomers (see Experimental). In this case, the preferential formation of a 5-membered oxazolidinone ring system apparently indicated that this process (5-Exo-Trig 9) ring closure) is more favorable than that of 6-membered ring derivative 3 by 6-Exo-Trig ring closure. The fact that the 6-membered ring system can be isolated easily in the reaction of a noncompetitive cyclization system, i.e., the formation of compound (5) 10) from the start- Preferential Intramolecular Ring Closure of Aminoalcohols with Diethyl Carbonate to OxazolidinonesFumiko FUJISAKI, Marumi OISHI, and Kunihiro SUMOTO* Science, Fukuoka University; Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Received January 19, 2007; accepted February 22, 2007 The closure by cyclization with diethyl carbonate (EtO) 2 CO from aminoalcohols 1 as starting material can lead to the oxazolidinones 2a, b and 2c, respectively. In the reaction of trans-isomer (6) and (EtO) 2 CO, isolated products were also only 5-membered oxazolidinone derivative (7), containing its deh...

show abstract

“…2) One of the applications of this unique amino acid for the synthesis of N- [2-(1-piperidinyl)ethyl]benzamides (2) has been reported recently.…”

mentioning

confidence: 99%