13655-52-2Relevant articles and documents
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Simon et al.
, (1974)
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Continuous flow upgrading of glycerol toward oxiranes and active pharmaceutical ingredients thereof
Morodo, Romain,Gérardy, Romaric,Petit, Guillaume,Monbaliu, Jean-Christophe M.
, p. 4422 - 4433 (2019/08/21)
A robust continuous flow procedure for the transformation of bio-based glycerol into high value-added oxiranes (epichlorohydrin and glycidol) is presented. The flow procedure features a central hydrochlorination/dechlorination sequence and provides economically and environmentally favorable conditions involving an organocatalyst and aqueous solutions of hydrochloric acid and sodium hydroxide. Pimelic acid (10 mol%) shows an exceptional catalytic activity (>99% conversion of glycerol, a high selectivity toward 1,3-dichloro-2-propanol and 81% cumulated yield toward intermediate chlorohydrins) for the hydrochlorination of glycerol (140 °C) with 36 wt% aqueous HCl. These conditions are validated on a sample of crude bio-based glycerol. The dechlorination step is effective (quantitative conversion based on glycerol) with concentrated aqueous sodium hydroxide (20 °C) and can be directly concatenated to the hydrochlorination step, hence providing a ca. 2:3 separable mixture of glycidol and epichlorohydrin (74% cumulated yield). An in-line membrane separation unit is included downstream, providing usable streams of epichlorohydrin (in MTBE, with an optional concentrator) and glycidol (in water). The scalability of the dechlorination step is then assessed in a commercial pilot-scale continuous flow reactor. Next, bio-based epichlorohydrin is further utilized for the continuous flow preparation of β-amino alcohol active pharmaceutical ingredients including propranolol (hypertension, WHO essential), naftopidil (prostatic hyperplasia) and alprenolol (angina pectoris) within a concatenable two-step procedure using a FDA class 3 solvent (DMSO). This work provides the first example of direct upgrading of bio-based glycerol into high value-added pharmaceuticals under continuous flow conditions.
Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 3899 - 3908 (2015/02/19)
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
ANTIHYPERTENSIVE THERAPY
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, (2009/09/08)
A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.