Chapter 6, Problem 53P

(a)

Interpretation Introduction

Interpretation:Part of the sanjoinine molecule that is derived structurally from $\left(\text{2S,3S}\right)\text{-3-hydroxyleucine}$ should be determined.

Concept introduction:Peptides are defined as smaller fragment of amino acids that are linked by special peptide linkage that is essentially an amide $-\text{NH}-$ bond. They are often categorized on the basis of number of amide bonds. For instance, a dipeptide has two amino acid residues linked via amide bond. Similarly tripeptide, tetrapeptide consists of three and four amino acids residues respectively. Peptides chains can be increased in length by addition of amino acid residue. Whilefor formation of amide bond, water is liberated when N−terminal condenses with C terminal of amino acid.

(b)

Interpretation Introduction

Interpretation: Four diastereomers of $2-bromo-3-hydroxy-4-methylpentanoicacid$ should be drawn and the one that would be the best starting material for a preparation of (2S,3S)-3-hydroxyleucine should be determined.

Concept introduction: Bimolecular substitution or ${\text{S}}_{\text{N}}2$ proceeds via single-step mechanism. Thus it is well known as concerted mechanism. Nucleophile approaches carbon while the leaving group still departs from the rear side (opposite to leaving group). The transition state only illustrates the geometric orientation of the substrates and reagents as they pass through the maxima in the single-step mechanism.

A general ${\text{S}}_{\text{N}}2$reaction mechanistic pathway is illustrated below:

  

${\text{S}}_{\text{N}}2$ pathway as it is a stereospecific reaction. This essentially means the R stereoisomer can only lead to inverted S stereoisomer and vice versa. Thus the outcome is the rear side displacement of leaving group.

Polar-aprotic solvents accelerate the rate of ${\text{S}}_{\text{N}}2$ reactions. These solvents possess partial positive and negative charges also. However, they do not liberate any proton to the substrate unlike water, methanol solvents. Acetone, DMSO, THF or DMF are categorized as polar aprotic solvent.