Spatial Arrangement and Preparative Organic Synthesis

Abstract

As can be seen from the above scheme, the compounds (70) and (71) are also obtained as by-products in the synthesis of ynamines from t-butylchloroacetylene and trimethylamine (which is described in Section 3.4.). On slow addition (to avoid amide chloride formation and side reactions) of strong acids to the ynamine (72), the only product formed in the presence of tertiary amines, e.g. dimethylaniline, is the saIt (73) The cyclobutene cyanine can be readily synthesized in the presence of HBF4 even without special precautions [49,611, possibly because the weakly nucleophilic BF4Q anion makes the conversion of the keteneiminium structure (65) into the less polar enamine structure (66) impossible.A number of phenylethynyldialkylamines react smoothly with strong acids to form the corresponding cyanines, which can be converted into bromine derivatives (73) by treatment with N-bromosuccinimide (NBS); (73) can also be obtained by direct bromination of the ynamine in dioxane [53J:Bromination of the t-butylethynylamines instead of the phenyl compounds leads to :only the allene aniidinium salts (74) in yields of up to 87 %; this is apparently due to steric factors 1531. From a technical or economic point of view the total synthesis of sterically intricate. carbon compounds has become so important that a new field of preparative stereochemistry has been established which embodies a number of specially developed techniques. This is especially the case in the syntheses of alkaloids and antibiotics, and above all in the plant-scale production of hormonal steroids [I].

Finding the K best synthesis plans

“…They both focus on graph based descriptions of synthesis plans, and on formal quality measures of these plans. Hendrickson [ 8 ] models synthesis plans as binary trees, and defines quality measures based on convergency [ 21 ], which essentially is how balanced the tree is. The rationale for this quality measure is that the more balanced the tree for a plan is, the fewer reactions the average starting material will take part in, either directly or as part of larger molecules in later reactions.…”

“…When modeling synthesis plans as unary-binary trees, this is the sum of the lengths of all root-to-leaf paths, which is also known as the external path length of the tree. This measure optimizes the convergency [ 21 ] of the plans: fully convergent plans (balanced trees) minimizes , whereas linear plans maximizes it. The measure aims at reducing overall loss of material during the synthesis by reducing the number of reactions in which the average starting material takes part.…”

Efficient Chemical Protein Synthesis using Fmoc‐Masked N‐Terminal Cysteine in Peptide Thioester Segments

“…[5b] In convergent synthesis, two halves of the polypeptide chain, synthesized independently in parallel from two or more peptide segments using NCL, are joined in a final step to give the full-length polypeptide chain. Fully convergent chemical syntheses are always efficient in terms of purity and yield; [6] and have been widely applied for the synthesis of number of large protein molecules. [5] Both one-pot multisegment ligation from the C-terminal peptide segment towards the N-terminal segment and fully convergent synthesis mandate temporary protection of the reactive cysteine residue located at the N-terminus of middle peptide thioester segment(s).…”

Metallacycle-mediated cross-coupling in natural product synthesis

“…Convergency is among the most important strategic considerations in complex molecule synthesis, as it provides a means to decrease the longest linear sequence of chemical transformations required to convert simple starting materials into complex structures. 3 Because yields of organic reactions are typically less than quantitative, significant contraction in the length of such sequences used to prepare a target can have a profound impact on efficiency. Of additional value, points of convergency in a synthesis pathway offer opportunities to introduce structural variation in a straightforward fashion – a feature of relevance in medicinal pursuits.…”