Maria Antonietta Loreto

Two new stereochemically complementary oxindole synthesis

Two routes have been developed for the conversion of ketones to oxindoles in the general sense (3 → 4); with norbornanone, the two routes gave different oxindoles (22 and 4).

Two new oxindole syntheses

Two oxindole syntheses are described, both starting from ketones, in which the carbonyl carbon becomes C-3 of the oxindole. The first route uses o-lithioformanilide followed by attack with cyanide ion and hydrolysis. The second uses a pinacol-type rearrangement (or the γ-silyl alcohol variation) to create the quaternary centre, and involves an intramolecular displacement of fluoride ion from an unactivated benzene ring by an amide nitrogen to complete the lactam ring. The two routes are stereochemically complementary, giving different spiro-oxindoles from norbornanone.

The Suzuki Reaction Applied to the Synthesis of Novel Pyrrolyl and Thiophenyl Indazoles

The paper describes the Suzuki cross-coupling of a variety of N and C-3 substituted 5-bromoindazoles with N-Boc-2-pyrrole and 2-thiopheneboronic acids. The reactions, performed in the presence of K2CO3, dimethoxyethane and Pd(dppf)Cl2 as catalyst, gave the corresponding adducts in good yields. The methodology allows the facile production of indazole-based heteroaryl compounds, a unique architectural motif that is ubiquitous in biologically active molecules.

Stereochemistry in reactions of chiral cyclic allylsilanes with (ethoxycarbonyl)nitrene. A new route to chiral N-substituted allylamines

Abstract The S E . reactions of chiral cyclic allylsilanes with (ethoxycarbonyl)nitrene generated by α- elimination of NsONHCO 2 Et with Et 3 N permit us to obtain chiral N -substituted allylic amines in good diastereomeric excess when stereoelectronic and conformational factors allow the anti attack.

Targeting Serotonin 2A and Adrenergic α1 Receptors for Ocular Antihypertensive Agents: Discovery of 3,4-Dihydropyrazino[1,2-b]indazol-1(2H)-one Derivatives

Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α1) linked to the regulation of aqueous humour dynamics. Herein we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic N2‐alkyl‐indazole‐amide derivatives. This study identified a 3,4‐dihydropyrazino[1,2‐b]indazol‐1(2H)‐one derivative with potent serotonin 2A receptor antagonism, >100‐fold selectivity over other serotonin subtype receptors, and high affinity for the α1 receptor. Moreover, upon local administration, this compound showed superior ocular hypotensive action in vivo relative to the clinically used reference compound timolol.

Spiroaziridines from 4-Substituted alpha -ylidene-gamma-butyrolactones

4-Substituted a-ylidene-y-butyrolactones produce N-ethoxycarbonyl-spiroaziridino γ-lactone diastereomers on treatment with NsONHCO 2 Et and CaO. A good stereofacial preference is observed when the ring substituent is a phenyl group. These products are precursors of α-aminolactone as pure diastereomers.