Retrosynthetic analysis equivalents

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Retrosynthetic analysis may identify a need to use synthetic equivalent groups. These groups are synthons that correspond structurally to a subunit of the target structure, but in which the reactivity of the functionality is masked or modified. As an example, suppose the transformation shown below was to be accomplished. 

A) Synthesis of A ring system Retrosynthetic analysis of cyclohexanone 2a leads to diene 5 and 2-chloroacrylonitrile 6 as a ketene equivalent (Scheme 13.6.2) as the starting materials. 

Let us consider the decomposition of formaldehyde cyanohydrin (2-hydroxyacetonitrile) into formaldehyde and hydrogen cyanide which is equivalent to the retrosynthetic analysis. The corresponding BE-matrices and the R-matrix are ... 

Systematic bond disconnection of porantherine [151] with recognition of the double bond-carbonyl equivalence for synthesis generated a synthetic pathway which is based on two intramolecular Mannich reactions. The symmetrical nature of the amino diketone precursor identified by the retrosynthetic analysis facilitates its preparation and subsequent transformations. Moreover, all the hetero atoms (donors) are separated by odd-numbered carbon chains and such arrangements are most amenable to normal modes of assembly. 

Scheme 3 illustrates retrosynthetic analysis of the E and F series of PGs. The widely used Corey synthesis (2) takes notice of the presence of the two olefinic bonds in the side chains of PGF2a. The actual synthesis consists of a two-fold Wittig-type chain extension of a chiral dialdehyde equivalent with four defined stereogenic centers derived from cyclopentadiene via a series of bicyclic intermediates. A similar sequential synthesis has been developed at Upjohn Co. (la). These chemical syntheses are much more economical than enzymatic methods and are used for commercial synthesis of certain PGs. An alternative pathway pioneered by Sih is the conjugate addition approach (3). Nucleophilic addition of an E-olefinic co side-chain unit to a cyclopentenone in which the a side chain is already installed leads directly to PGE-type compounds. Untch and Stork used an co chain unit with a Z-olefinic bond (4). The most direct and flexible synthesis is the convergent three-component coupling synthesis via consecutive linking of the two side chains to unsubstituted 4-hydroxy-2-cyclopentenone derivatives (5, 6). 

A retrosynthetic analysis of an a,/J-unsaturated aldehyde or ketone involves an initial functional group interconversion into a /1-hydroxycarbonyl compound, followed by a disconnection into the carbocation (12) and the carbanion (13) synthons. The reagent equivalents of these two synthons are the corresponding carbonyl compounds. 

A retrosynthetic analysis for this latter compound (as shown below) shows that it could arise from ethylene oxide [reagent equivalent to (5), see Section 5.4.2, p. 533], and ethyl acetoacetate [reagent equivalent to (6), see Section 5.8.5, p. 619],... 

This time-honoured view of ring construction preceded the retrosynthetic approach it is still of value since it provides an indication of which bonds could be selected for disconnection. The more rigorous application of the principles of retrosynthetic analysis leads of course to the formulation of synthons and their reagent equivalents. 

A retrosynthetic analysis for coumarin reveals salicylaldehyde and acetic anhydride (under basic conditions) as suitable reagent equivalents of the derived synthons. 

Retrosynthetic Analysis — One-Step Disconnections. For each of the following compounds, suggest a one-step disconnection. Use FGIs as needed. Show charge patterns, the synthons, and the corresponding synthetic equivalents. 

Retrosynthetic analysis. Outline a retrosynthetic scheme for the following target molecules. Show (1) the analysis (including FGI, synthons, synthetic equivalents) and (2) the synthesis of each TM. You may only use compounds with five or fewer carbons as starting materials. 

Linalool is another perfumery compound. Disconnection of the vinyl group leads to the ketone you met on p. 787, best made by alkylation of acetoacetate, an acetone enolate equivalent, linalool retrosynthetic analysis... 

Inspired by the biosynthesis of carbohydrates we envisaged a direct de novo synthesis of carbohydrate derivatives by using the DHA-equivalent 4 in a C3+Cn-sirategy. As can be seen from the retrosynthetic analysis, the desired building blocks 5 should be prepared from the dioxanone (4) and an aldehyde component 6 in an organocatalytic aldol reaction... 

Retrosynthetic analysis involves the disassembly of a TM into available starting materials by sequential disconnections and functional group interconversions. Structural changes in the retrosynthetic direction should lead to substrates that are more readily available than the TM. Synthons are fragments resulting from disconnection of carbon-carbon bonds of the TM. The actual substrates used for the forward synthesis are the synthetic equivalents (SE). Also, reagents derived from inverting the polarity (IP) of synthons may serve as SEs. 

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