- Sequential alcohol oxidation/putative homo Claisen-Tishchenko-type reaction to give esters: A key process in accessing novel biologically active lactone macrocycles
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We report an efficient methodology for the direct oxidative esterification of primary alcohols to diether-esters using pyridinium chlorochromate (PCC). Numerous studies were carried out to probe the reaction mechanism and at the same time optimize the reaction conditions. The reaction could be conducted with 1 equivalent of PCC and 1 equivalent of BF3·OEt2. Indications based on literature precedent were that the reaction may proceed via a sequential alcohol oxidation to the aldehyde followed by a putative Cr or boron catalyzed Claisen-Tishchenko-type reaction. Using this efficient methodology, we synthesized a family of novel diether-esters in very good yields; some of these molecules were subsequently tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In addition, we also disclose a new synthetic strategy for the synthesis of lactam macrocycles with potential biological activity. This methodology included the regioselective borylation of the ester substrate and a subsequent Suzuki-Miyaura coupling to obtain the desired lactam macrocycle.
- Viana, Hugo,Carreiro, Elisabete P.,Goth, Albertino,Bacalhau, Patrícia,Caldeira, Ana Teresa,Do Rosário Martins, Maria,Burke, Anthony Joseph
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p. 63214 - 63223
(2016/07/19)
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- Intermediates for macrocyclic compounds
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The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R1, R2, R3, R4, R5, R6, n1, m, p Z1, Z2, and Z3 are as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.
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Page/Page column 31; Sheet 5
(2015/11/30)
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- Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
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Compounds of the general formula (I): wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT2receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2creceptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders.
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