Cubane derivatives 10. Synthesis and molecular structures of nitroxymethylcubanes

Abstract

The reactions of hydroxymethylcubanes with nitric acid result in the respective nitroxy methylcubanes.The search for the drugs to treat cardiovascular and oncological diseases is currently highly topical. The prepa ration of new polyfunctional compounds, study of their structures and properties will allow expansion of the spec trum of exogenous NO donors as potential drugs.Nitrates (or nitroesters) are a well known class of or ganic substances the pharmacological activity of which is determined by their metabolism with NO liberation (see Ref. 2). They include such compounds as Nitroglycerin, Nitrosorbide, Erinite, and others, which are commonly * For Part 9, see Ref. 1. † Deceased. Scheme 1used to treat ischemic cardiovascular diseases, for ex ample, stenocardia. It is known that cubane derivatives also show rather high anti ischemic activity. 3,4With the aim of search for new anti ischemic drugs, we performed the synthesis of nitroesters of the cubane series.Previously, 5,6 it has been shown that the reduction of dimethyl cubane 1,4 dicarboxylate (1a) and methyl 4 bromocubane 1 carboxylate (2) afforded 1,4 bis (hydroxymethyl)cubane (3) and 4 bromo 1 hydroxy methylcubane (4). In the present work, 1,4 bis(nitroxy methyl)cubane (5) and 4 bromo 1 nitroxymethylcubane

Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes

“…This allows the bromine atoms to interact with the hydrogen of the cubane in the next layer to create a 3D lattice. When substituting hydroxymethyl for a methyl nitrate ( 51 ) the NO 2 group interacts with the cubane the CH 2 hydrogen atoms . This leaves bromine atoms close to each other to form a direct halogen‐bonded network (Figure S24).…”

“…(Figure 5, bond lengths and angles are given in Table S1). [6,12] In these compounds (also for the carboxamides ande sters sections below) hydrogen bondingi so ne of the main driving forces seen in the packing.H ydrogen bonding is defined (by IUPAC standards) as an attractive interaction between ah ydrogen atom from am olecule or am olecular fragment that is more electronegative and an atom or group of atoms in the same or different molecule where there is evidence of bond formation. [13] The bond distance is typically less than or equal to the sum of the van der Waals radii of the atomsi nvolved and the anglesd epend on the atoms involved.…”

“…As highlighted by Fleischer et al the bent bonds of cubane scaffold allow for the acidic hydrogen atomst ob ep resented in severald irections which are unavailable for its benzene counter-part. [15] However,t his effect is only [6,12] seen in certain cubane carboxylic acids (3-6, 9 and 10). It can be seen that the 4-substituted position to the cubanes caffold plays an important role in the formation of catemers.…”

“…Thefirst is the dimer formed between the CH 2 hydrogens with the terminal nitrogeno ft he azide group. The second is the linear network formed between the cubane hydrogen interacting nitrogen atom connected to the carbon skeleton ( Figure S15 The final group of the esters features new compounds recently published by our group (40) [3a] and severald etermined as part of this work (12,(41)(42)(43)(44) ( Figure 12, Ta ble S5). The structure of 40 is an interesting example of what occurs when an extendedr igid arm is present in the 4-position of am ethyl ester cubane.…”

Preparation of quaternary ammonium salts with a perhydroimidazo[1,5-c]oxazolium molecular skeleton

“…In the CH 2 ONO 2 group (compound 1) and in the CH 2 OH group (com pound 8), the observed magnetic nonequivalence (0.05 and 0.12 ppm, respectively) is typical of such compounds. 6 Cyclisation with formation of rifid structures 6 and 7 makes all gemi nal positions nonequivalent. Hence a complex overlap ping AB type pattern is observed at δ 3.5-5.1, as well as poorly resolved (even on a 500 MHz instrument) piperi dine ring multiplets at δ 1.5-3.8 in compound 6 and two methyl group singlets in compound 7 that became non equivalent are observed.…”