Stable conformation

The l-rcrt-butyl derivative 9 can be obtained in an optically active form even though the compound contains no asymmetric carbon atom. The chirality is due to the nonplanarity of the seven-mem be red ring, which is conformationally stable.191... 

A different strategy for the development of carbohydrate mimics has focused on the replacement of the non-pharmacophoric parts of active oligosaccharides by conformationally stable cyclic diols. Thus, looking for an analogue of the a-o-Man/)-(l — 2)-a-D-Man/>-(l — 6)-a-D-Man/)-mannotrioside, one of the terminal arms of the MangGlcNAc2... 

Neupogen), a four-helix bundle cytokine, is formulated at pH 4 but has been shown to maintain both thermal stability and tertiary structure at pH 2.60 In fact, the secondary structure of this molecule was shown to remain highly helical at pH 4 (Tm approximately 62°C) and 2 (Tm approximately 63°C) as compared to pH 7 (Tm approximately 55°C) where a less conformationally stable form was observed. In the same study, FTIR and CD data corroborated the tendency of the protein to unfold as measured by the loss of helical structure in the order pH 7 > pH 4 > pH 2. Moreover, after determining optimal pH conditions of thermostability, several studies have shown that excipient screening at such conditions can successfully predict the rank of formulation cocktails that offer the most favorable stability.14 23 31 56... 

Later methods of stereoselective synthesis of alkaloids 30, 31 and their derivatives differ mainly in the construction of the conformationally stable intermediate with a 3-(2-piperidyl) substituted indole fragment (type 38). In the... 

With regard to the distinctly different activities of the a- and /3-D-linked maltosyl trehalose tetrasaccharides, it is interesting to note that highly sulfated a-D-linked glucosides were conformationally stable whereas the -o-linked glu-... 

The complexes Mo(CO)4(R-DAB) are not conformationally stable, as indicated by 13C NMR spectroscopy which shows cis-trans exchange of the carbonyl ligands, probably via a transition state with pseudo C4, symmetry.133... 

Even though the carbanion is not configurationally or conformationally stable, it will prefer an arrangement with the R-groups further apart that will later lead to the ( )-alkene ... 

Very recently, Stahl et al. reported the first synthesis of a 7-membered NHC ligand [98]. Despite substantial effort, the isolation of the free carbene 21 was not successful. However, palladium complexes of 21 could be formed and structurally characterized. Ligand 21 is C2 symmetric as a result of a torsional twist which is thought to attenuate the antiaromatic character of the 87r-electron carbene heterocycle [101,102]. It will be interesting to see, if the synthesis of conformationally stable analogues and their application in asymmetric catalysis will be feasible. 

The H—NMR-spectra of 21 resp. 22 remain unchanged up to at least 175 °C resp. 130 °C. This indicates a high conformational stability of the two phanes. The molecular propellers 45 21 and 22 belong to point group D3. Organic chemistry up to now only knows of four conformationally stable structures of this symmetry46-49. ... 

This is because the mechanism of reduction proceeds through a planar radical D that can rotate freely about the carbon-carbon bond (Scheme 4.33). Thus, both diastereomers C would pass through the same radical intermediate, which can be used to explain the -selectivity. Even though the carbanion E is not configurationally or conformationally stable, it will prefer an arrangement with the R groups further apart that will later lead to the -alkene. 

In the triphenyhnethanides, the metal is coordinatively and electronically saturated by the encompassing crown ether that occupies an equatorial plane around the metal, as well as by the axially located HMPA donors. This favorable cation coordination enviromnent is well established in alkaline earth metal chemistry. The hgands are free to adopt the most conformationally stable orientation, and steric demands force the rings away from planarity and in both the strontimn and barium systems the rings display the familiar propeller geometry, comparable to that seen for related alkali systems. 

Similar conditions for the formation of a (Z)-configured ketone enolate (6) at low temperature were applied by Myles and coworkers in their total synthesis of (-l-)-discoder-molide (10, equation 3f. Deprotonation of the ethyl ketone 7 with LiHMDS as base at —78 °C and addition of TMEDA delivered a (Z)-configured enolate (8), which was subsequently alkylated with allyl iodide 9. Thereby, chelation of the lithium enolate with the adjacent MOM protecting group led to a conformationally stable chair-like transition-state 8, in which the attack of the alkylation reagent 9 (represented in 8 by E+) could only occur from the site opposite to the bulky group R. Thus, the alkylation prodnct 10 was obtained with a good diastereomeric selectivity at C of 83-85% ds. 

The Ti —To-value can be regarded as an approximate measure of -electron delocalization in annelated annulene rings. The above-mentioned results obtained on conformationally stable annelated acetylcne-cumulene dehydroannulenes seem to give the following conclusions ... 

In cyclohexane chemistry, a t-butyl group that occupies an equatorial position can function as a holding group. Substitution of a t-butyl group in the 4-position relative to the heteroatom has been successfully utilized to prepare conformationally stable derivatives of both sila-... 

Triazolines with secondary or tertiary amino groups in the 4 position were similarly made by treating a primary or secondary amine (respectively) with an aldehyde or ketone and p-nitrophenyl azide in chloroform (25°C, 1-14 hr, 30-98%) (64JA2213 69G1131). The products isolated from chloroform were usually mixtures of cis and trans isomers [as determined by NMR (See Section II,D)], whereas recrystallization from benzene gave the pure trans isomer, which was conformationally stable only if a bulky group, such as phenyl, occupied the 5 position [72JCS(P1)997]. 

To be successful in these applications, it is important that materials can self-assemble into precisely defined structures. Peptide polymers have many advantages over conventional synthetic polymers since they are able to hierarchically assemble into stable ordered conformations [4]. Depending on the amino acid side chain substituents, polypeptides are able to adopt a multitude of conformationally stable regular secondary structures (helices, sheets, turns), tertiary structures (e.g. the /J-slrand-helix-/J-strand unit found in /1-barrels), and quaternary assembhes (e.g. collagen microfibrils) [4], The synthesis of polypeptides that can assemble into non-natural structures is an attractive challenge for polymer chemists. 

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