Synthetic Approaches to Non-Tropane, Bridged, Azapolycyclic Ring Systems Containing Seven-Membered Carbocycles

This Short Review highlights various synthetic approaches to bridged azabicyclic ring systems containing seven-membered carbocyclic rings. Such ring systems are common to a number of biologically active natural products. The seven-membered ring in such systems is generally formed in one of four ways: 1) cyclization of an acyclic precursor; 2) ring expansion or rearrangement of a different ring size; 3) cycloaddition; and 4) use of a synthetic building block with the seven-membered ring already present. Representative examples of each approach from both total synthesis and methodological studies are discussed, with an emphasis on work publishedin the last twenty years.1 Introduction2 Cyclization Reactions3 Ring Expansions and Rearrangements4 Cycloadditions5 Strategies Involving Seven-Membered Ring Building Blocks6 Conclusion

COMPARATIVE ANALYSIS OF ANTI-INFLAMMATORY AND ANALGETIC ACTIONS OF 1,3-DIAZINO-4 COMPOUNDS PYATd1 ACYCLIC PRECURSOR AND DAPSON

In the experiment performed on 144 Wistar male rats, the anti-inflammatory activities of a new diazinone derivative under the code of PYATd1 and dapsone, were studied in the model of acute exudative and chronic proliferative inflammation. The analgetic activity was studied by mechanical irritation against the background of formalin sia. The results obtained indicate that the compound PYATd1 has pronounced anti-inflammatory and analgetic effects, superior to dapsone and comparable to ibuprofen, diclofenac and nimesulide.

An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

<p>Abstract: Herein, we report further improvements to the synthesis of tenofovir <b>1</b>, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile <b>12</b>, a four-step protocol to tenofovir <b>1 </b>will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from <b>6</b> as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium <i>tert</i>-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.</p>

An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

<p>Abstract: Herein, we report further improvements to the synthesis of tenofovir <b>1</b>, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile <b>12</b>, a four-step protocol to tenofovir <b>1 </b>will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from <b>6</b> as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium <i>tert</i>-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.</p>

Palladium-Catalyzed Formation of Substituted Tetrahydropyrans: Mechanistic Insights and Structural Revision of Natural Products

A comprehensive study on the stereochemical outcome of palladium-catalyzed formation of 2,4,6-trisubstituted tetrahydropyrans through cyclization of the corresponding allylic acetates using both Pd(0) and Pd(II) catalysts is presented. We have found that the stereochemical outcome of this cyclization is dependent not only on the ­stereochemistry of the acyclic precursor but also on the nature of the palladium catalyst. These results were applied to the total synthesis of the putative structure of cryptoconcatone H. Experimental and computational DP4+ NMR results were used to assess the structures proposed for cryptoconcatones K and L.

[E(μ-NBbp)]2 (E = P, As) – group 15 biradicals synthesized from acyclic precursors

Starting from an acyclic precursor R–N(ECl2)2, the preparation of biradicals of the type [E(μ-NBbp)]2 (E = P, As) was achieved.

Total Synthesis of Cordyheptapeptide A

The first total synthesis of cordyheptapeptide A is described. The synthesis is accomplished by a convergent approach featuring a combination of peptide coupling and the Ugi reaction for the preparation of the main building blocks and the acyclic precursor. The assembly of an N-methylated fragment by the Ugi reaction comprised the utilization of a convertible isonitrile followed by activation of the C-terminal amide. Two different macrocyclization sites were evaluated, proving greater efficacy the macrolactamization at the site Ile-Tyr, likely due of a more suitable conformational bias of the acyclic precursor having an internal β-turn centered at the N-Me-d-Phe-Pro moiety.