Synthesis Outline

4-methylbenzenesulfonic acid Molecular Formula = C HgO S Formula Weight = 172.20162 

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The actual process of solid phase peptide synthesis outlined m Figure 27 15 begins with the attachment of the C terminal ammo acid to the chloromethylated polymer m step 1 Nucleophilic substitution by the carboxylate anion of an N Boc protected C terminal... 

The multistrategic retrosynthetic analysis of retigeranic acid, which led to the synthesis outlined below, has been described in Section 6.6 of Part One. 

Diisocyanoadociane, a novel marine-derived diterpenoid, was analyzed retrosynthetically using the intramolecular Diels-Alder transform as T-goal concurrently with topological and stereochemical guidance. The enantioselective synthesis outlined below allowed assignment of absolute configuration. 

Khellin is a natural product closely related to the psoralens in which a chromone ring has been substituted for the cou-marin. The plant material has been used since ancient times as a folk remedy modern pharmacologic work has confirmed the bronchio-dilating and antispasmodic activity of khellin. The synthesis outlined below, it should be noted, is selected from a half-dozen or so reported within the last quarter century. 

The synthesis outlined in Scheme 13.72 was carried out by James Panek s group at Boston University and is based on three key intermediates that were synthesized from two closely related methyl 3-(dimethylphenylsilyl)hex-4-enoates. 

Proof of Constitution.—Very little reliable evidence regarding the position of the ether group in 2-methyl-D-glucose is available from the methods of synthesis outlined above. In some cases9 1013 the structures... 

Ring closure y to a heteroatom is also a rather uncommon [5 + 1] procedure although there are some important exceptions. The most widely investigated is the Bernthsen acridine synthesis in which a diarylamine is condensed with a carboxylic acid in the presence of a Lewis acid (equation 73). More recently, it has been shown that acylanilines react with the Vilsmeier-Haack reagent to give quinolines in good yield (e.g. equation 74) and the mechanism of the reaction has been elucidated. A final example of [5 +1] ring closure y to a heteroatom which is of occasional use is the pyrazine synthesis outlined in equation (75). 

The general methods of synthesis outlined below are merely a collection of simple, common sense, practical techniques presented in an organized manner. Some of the methods will already be familiar to you from previous experience, and you will probably gain experience in additional methods as you progress through your present chemistry course. 

Both the fungus Eremothecium (Box 15-B) and mutants of Saccharomyces have been used to deduce the pathways of riboflavin synthesis outlined in Figure 25-20. The first reaction (step a) is identical to step a of Fig. 25-19 but is catalyzed by a different GTP cyclohydrolase.362 Instead of an Amadori rearrangement it catalyzes the hydrolytic deamination and dephosphorylation (step b) to give the flavin precursor... 

The first total synthesis of a phallotoxin was that of norphalloin, the norvaline analogue of phalloidin.16 This synthesis, outlined in Scheme 2, initially involves the synthesis of two building blocks followed by their covalent binding via a tryptathionine moiety. Subsequent deprotection and coupling steps using classical methods of peptide synthesis results in the formation of norphalloin, which has proved to be even more toxic than the natural toxins. Since the synthesis of norphalloin, a number of synthetic analogues have been synthesized in order to obtain information on structure-activity relationships.[7 8]... 

Scheme 38 Synthesis Outline of the Linear Precursor of Omphalotin Ai401...

However, when it comes to thiopyrones an enormous range of substituents is known and almost any of the methods of ring synthesis outlined above may be used. It is especially easy to set up ambident nucleophilic species such as (143) which may be S-alkylated to (144). Thermolysis isomerizes such compounds to the 4,6-bis(alkylthio) analogues the rearrangement has been thoroughly investigated (67JOC3140). 

The synthesis of the thioaldehyde complex 63 somewhat paralleled the synthesis outlined in Scheme 17. In this case, sulfur and hydrogens were transferred to the vinylidene ligand in a single step [Eq. (14)].187... 

Synthesis. Outline a retrosynthetic scheme for each of the following target molecules using the indicated starting material. Show (1) the analysis (including FGI, synthons, and synthetic equivalents) and (2) the synthesis of each TM. 

In regard to third-party collaboration in the manufacture of Schering-Plough s antibiotic, Florfenicol (XVII), the initial thrust by our Animal Health Division, developers of the molecule, was to involve a third party with an excellent track record in another project with them. The third party partially explored the synthesis outlined in Scheme 6. 

When the synthesis outlined in Scheme 5.17 was applied to larger loops (e.g., n = 20), the purification of the product became more difficult or even impossible. While the samples showed the expected ESI mass spectrum, a satisfactory purification from a chromatographically similar compound was not possible, and the 1H NMR spectrum was not entirely in agreement with the expected structure. This led... 

The stoichiometry of the synthesis outlined in Figure 5.63 may well be confusing at first, but will unfold in a very simple manner when we reconstruct the details of the reaction given in this figure. The following partial reactions are involved ... 

The method to be described is a significant modification of the synthesis outlined by Hurd and Brimm2 and is derived from the apparatus of Geilmann and Wrigge.6 This procedure allows for the decomposition of large quantities of rhenium(V) chloride in a short period (approximately an hour for a 14-g. sample), in high yield (of the order of 90%) and by an inexperienced person. 

Conclusions Both Right and Wrong. Basically these results support a specific attack of the enzyme on the sn-2 ester bond, and certainly the release of a specific fatty acid would support such a conclusion. Earlier proof that the phospholipase A2 prefers the sn-3 configuration and will not attack the sn-1 form allows one to be quite comfortable in a decision on its stereospecificity. Yet, no where here has it been proven unequivocally that the partial synthesis outlined in Figure 4-11 above does give the fatty acids substituted in the described positions. The only route to such proof is through the use of de novo synthesis as discussed above. This approach will allow one to make claims as to the position of fatty acids on phosphoglycerides. 

PROBLEM Summarize the synthesis outlined in the problem-solving strategy. This summary should be in the synthetic (forward)... 

The unsaturated amine A, a useful intermediate in the synthesis of the atnaryllidaceae (daffodil) alkaloids, can be made from the three starting materials shown below. What kind of chemistry is required in each case Which is best adapted for asymmetric synthesis Outline your chosen synthesis. 

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