Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• progestogen activity, so it is employed in combination with ethinylestradiol in oral contraceptives [6]. Various steroidal spiro heterocycles serve as effective drugs for treating diverse pathologies. For example, cyclopamine (Figure 1) inhibits Hedgehog (HH) signaling by interacting with the 7-transmembrane

• illustrate that a spirocycle can alter the stability, physicochemical, and pharmacokinetic properties of the structure [9]. In this review, we summarize recent synthetic procedures reported between 2000 and 2023 for synthesizing steroidal spiro heterocycles. The review categorizes the procedures based on the

• -ones (spirocarbamates). These spiro heterocycles are commonly obtained in good yields through treatment with triphosgene and DIPEA. In the last decade, Poirier’s group reported a synthetic strategy to produce several spiro derivatives as discovery platforms for new bioactive compounds (Scheme 20) [39

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• experimentally observed stereoselectivity. Keywords: azomethine ylides; cycloaddition; cyclopropenes; DFT calculations; spiro heterocycles; Introduction Spiro compounds (molecules containing at least two rings with only one common atom) are an important class of both synthetic and naturally occurring

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• rearrangement (PTR, Scheme 1) [8][9][10][11], which is a special case of a quite poorly investigated iminothiolactone–thiolactam rearrangement [12][13][14][15][16]. This reaction offers attractive opportunities for the design of libraries of regioisomeric hydantoin-based compounds for drug discovery. Spiro

• heterocycles are relatively new and insufficiently investigated structures in medicinal chemistry [17][18]. The introduction of spiro-fused cyclic moieties in small molecules increases the degree of their structural (shape) complexity, which may lead to the reduced binding promiscuity and improved clinical

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• olefinic terminal position remains unsubstituted to achieve these outcomes. The addition of substituents to the terminal positions of the allyl reagents (crotyl, 1,1-dimethylallyl, cinnamyl) resulted in a change in the major product outcome to the known spiro heterocycles 14, 15 and 16, although with a

• outcomes (Scheme 9). The first of these are the mono-N-allyindigos 2–6 which can branch to the synthesis of the spiro heterocycles 12–16 (Path A – which is a mechanistic sink). Alternatively, mono-N-allyindigos can progress to the synthesis of the azepinodiindolones 17 and 18 (Path B – also a mechanistic

• of 9 towards Vero cells [18] was attempted but its autofluorescence precluded a result being obtained. These spiro heterocycles, indoloazepinoindol-17-one and azepinodiindolo compounds constitute new antiplasmodial structural leads with potentially new modes of action. Modest cytotoxicity against all