17‐Oxo‐5α‐androstane‐3α,4β‐diyl diacetate and 17‐oxo‐5β‐androstane‐3α,4β‐diyl diacetate

The title compounds, both C₂₃H₃₄O₅, are the 5α and 5β configurations of two diacetate epimers. The 5β‐diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 ų, responsible for clathrate behaviour. The 5β‐epimer also features some shorter than average bond lengths in the 3α,4β‐acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through abinitio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C—H⋯O interactions.     

αvβ3‐ or α5β1‐Integrin‐Selective Peptidomimetics for Surface Coating

Engineering biomaterials with integrin‐binding activity is a very powerful approach to promote cell adhesion, modulate cell behavior, and induce specific biological responses at the surface level. The aim of this Review is to illustrate the evolution of surface‐coating molecules in this field: from peptides and proteins with relatively low integrin‐binding activity and receptor selectivity to highly active and selective peptidomimetic ligands. In particular, we will bring into focus the difficult challenge of achieving selectivity between the two closely related integrin subtypes αvβ3 and α5β1. The functionalization of surfaces with such peptidomimetics opens the way for a new generation of highly specific cell‐instructive surfaces to dissect the biological role of integrin subtypes and for application in tissue engineering and regenerative medicine.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

6β‐Azido‐7α‐hydroxy‐17‐oxo‐5α‐androstan‐3β‐yl acetate

In the title compound, C₂₁H₃₁N₃O₄, a potential inhibitor of aromatase, all rings are fused trans. Rings A, B and C have chair conformations which are slightly flattened. Ring D has a 14α‐envelope conformation. The steroid nucleus has a small twist, as shown by the C19—C10⋯C13—C18 torsion angle of 6.6 (2)°. Ab initio calculations of the equilibrium geometry of the mol­ecule reproduce this small twist, which appears to be due to the steric effect of the 6β‐azide substituent rather than to packing effects.     

Concise Synthesis of α‐Methylene‐β‐hydroxy‐γ‐carboxy‐γ‐lactams

A concise protocol for the synthesis of α‐methylene‐β‐hydroxy‐γ‐carboxy‐γ‐lactams has been described via alkylation of amino acid derived iminoesters with α‐bromomethylmethacrylate, followed by allylic hydroxylation. All the synthesized compounds have been evaluated for their cytotoxicity on multiple myeloma cancer cell lines.     

Reactions of 3‐methylamino‐5‐phenylthiophene with α,β‐unsaturated esters and α,β‐unsaturated nitriles

Treatment of 3‐methylamino‐5‐phenylthiophene with α,β‐unsaturated esters, i.e., methyl acrylate, (E)‐methyl crotonate, diethyl fumarate, diethyl maleate and ethyl propiolate, in tetrahydrofuran for several days at reflux gave 1‐methyl‐3,4‐dihydrothieno[2,3‐e]pyridin‐2‐ones 4 and/or 1‐methylthieno[2,3‐e]pyridin‐2‐ones 5 , depending on the structure of the esters. On the other hand, the same reactions with α,β‐unsaturated nitriles such as acrylonitrile and tetracyanoethene, gave the corresponding thiophenes 7 and 10 bearing 2‐cyanoethyl and 1,2,2‐tricyanoethenyl groups at C‐2, respectively. The reaction with (Z)‐1,2‐dicyanoethene under the same conditions produced the corresponding thiophene 9 bearing the 1,2‐dicyanoethenyl group and 1,2‐dicyano‐5‐methylaminobiphenyl.     

21α‐Fluoro‐7‐norvouacapane‐17β,21α‐lactone

The crystal structure of 21α‐fluoro‐7‐norvouacapane‐17β,21α‐lactone, C₂₀H₂₅FO₃, a new synthetic derivative of the diterpenoid 6α,7β‐di­hydroxy­vouacapan‐17β‐oic acid isolated from Pterodon polygalaeflorus Benth fruits, is described.     

Enantioselective Palladium‐Catalyzed Oxidative β,β‐Fluoroarylation of α,β‐Unsaturated Carbonyl Derivatives

The site‐selective palladium‐catalyzed three‐component coupling of deactivated alkenes, arylboronic acids, and N‐fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step‐economical approach to the stereoselective β‐fluorination of α,β‐unsaturated systems.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.     

13‐cis‐β,β‐Carotene and 15‐cis‐β,β‐carotene

13‐cis‐β,β‐Carotene, C₄₀H₅₆, crystallizes with a complete molecule in the asymmetric unit, whereas 15‐cis‐β,β‐carotene, also C₄₀H₅₆, has twofold symmetry about an axis through the central bond of the polyene chain. The polyene methyl groups are arranged on one side of the polyene chains for each molecule and the 6‐s‐cisβ end groups, with the cyclohexene rings in half‐chair conformations, are twisted out of the planes of the polyene chains by angles ranging from 41.37 (17) to 52.2 (4)°. The molecules in each structure pack so that the arms of one occupy the cleft of the next, and there is significant π–π stacking of the almost‐parallel polyene chains of the 15‐cis isomer, which approach at distances of 3.319 (1)–3.591 (1) Å.     

16α,17α‐Epoxy‐20‐oxopregn‐5‐en‐3β‐yl acetate

The title compound, C₂₃H₃₂O₄, has a 3β configuration, with the epoxy O atom at 16α,17α. Rings A and C have slightly distorted chair conformations. Because of the presence of the C5=C6 double bond, ring B assumes an 8β,9α‐half‐chair conformation slightly distorted towards an 8β‐sofa. Ring D has a conformation close to a 14α‐envelope. The acetoxy and acetyl substituents are twisted with respect to the average molecular plane of the steroid. The conformation of the mol­ecule is compared with that given by a quantum chemistry calculation using the RHF–AM1 (RHF = Roothaan Hartree–Fock) Hamiltonian model. Cohesion of the crystal can be attributed to van der Waals interactions and weak intermolecular C—H?O interactions, which link the mol­ecules head‐to‐tail along [101].     

5β,6β‐Epoxy‐17‐oxoandrostan‐3β‐yl acetate and 5β,6β‐epoxy‐20‐oxopregnan‐3β‐yl acetate

In the title compounds, C₂₁H₃₀O₄, (I), and C₂₃H₃₄O₄, (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis‐(5β,10β)‐fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5β,6β‐epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree–Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.