Mono-deprotected

Golebiowski et al. reported the solid-phase [92] and the solution-phase [93] syntheses of bycyclic diketopiperazines which were of great interest because their conformation was similar to the type-1 /i-turn motif. A Merrifield hydroxymethyl resin was esterified with a-N-Boc-fi-N-Fmoc-L-diaminopropionic acid and then mono-deprotected at the />-N with piperidine. Ugi-4CR of the resulting resin-bound amine gave the resin-bound adducts 168. Subsequent N-Boc deprotection and intramolecular N-alkylation afforded the ketopiperazines 169. The diketopiperazines 170 were formed via N-Boc amino acid coupling followed by N-Boc deprotection... 

Benzyl phosphates are less readily attacked by nucleophiles than methyl phosphates and they are more stable towards acidolysis than rm-butyl phosphates Benzyl phosphates are often used in complex polyfunctional targets because they are easily removed by hydrogenolysis. An indication of the reduced reactivity of benzyl phosphates is given in Scheme 7.17.32 Reaction of the phospho-nate diester 17.1 with one equivalent of 1 4-diazabicyclo[2 2 2]octane (DABCO) in refluxing toluene afforded the mono-deprotected derivative 17.2 in quantitative yield. Quinuclidine can also be used as the nucleophile. Assisted cleavage of benzyl phosphates is exemplified by the deprotection of the Shikimic Acid derivative in Scheme 7.18 using bromotrimethylsilane.33 34... 

The propionate derivative of oxazolidinone 214 was allowed to condensate with the aldehyde 215 to furnish 216 in 87% yield. Borohydride reduction of 216 gave diol 217. Selective tosylation of the primary alcohol resulted in spontaneous cyclization to give the pyrrolidinium tosylate salt, which was converted to its chloride salt 218 in 83% yield. Selective mono-deprotection of the salt afforded the free hydroxyl 219, which was acetylated and then subjected to hydrogenolysis in the presence IM hydrochloric acid to allow the isolation of the C(4)Me analogue 220 as its hydrochloride salt in quantitative yield. 

Condensation of 102c with symmetric or mixed (allyl, trimethylsilylethyl) ketomalonic esters gave the carbinolamides 283, which were reduced to 285 by chlorination (SOCl2/pyridine) and treatment with zinc (i-PrOH, AcOH in CH2CI2 concomitant TCE removal). The silver thiolates 286, obtained by tritylthio cleavage under the usual conditions, reacted with thiocarbonyldiimi-dazole to produce the cyclic compounds 288 directly. Mono-deprotection with... 

In 1969, Biichi et al. published the first total synthesis of racemic aflatoxin Ml (5) (36). They started with the diol 24, which was first dimethylated with dimethyl sulfate, then mono deprotected by aluminum chloride, and finally benzylated to afford species 25 (see Scheme 2.3). 

The synthesis of rac-versicolorin A (13) is shown in Scheme 2.18. Resorcinol (107) was MOM-protected and formylated to yield 108. Horner-Wadsworth-Emmons reaction with 109, followed by deprotection and reaction with ethyl bromoacetate gave, after hydrolysis, phenyl acetaldehyde 110. With TIPSOTf and triethylamine, cyclization occurred rapidly, followed by mono deprotection. 

Having precursor 407 in hand. Brooks et al. were able to synthesize anguidine (376) in a further 17 steps. Thus, precursor 407 was converted into enamine 409, which was hydrolyzed to hydroxymethylene derivative 410. Michael reaction with butanone afforded the exo product 411. Followed by an intramolecular Michael aldol condensation, enone 412 was obtained, which was methylated to the allyl alcohol 413 using methyl iodide. Subsequent reduction with Ufliium aluminum hydride led to tetraol 414. This was converted to the triacetate and selectively deprotected to diol 415. Acid-catalyzed cycUzation and protection of the free OH group afforded the trichothecene skeleton 416. Afterwards, the acetal 416 was deprotected and the ketone was reacted in a Wittig reaction to the olefin, which was treated with TBAF to afford compound 417. Epoxidation with /n-CPBA, followed by acetylatiOTi and final mono-deprotection, afforded the trichothecene, anguidine (376) (Scheme 8.4). 

A number of Lewis acid catalysts were screened for the above transformation and it was found that most could not completely deprotect the diacetate and instead formed the methyl ester and mono-deprotected acetate. However, none of the other catalysts tested generated the 5-lactone by-product (3), which was formed only when Z1CI4 was employed. The formation of this lactone by-product was the subject of further study due to the importance of lactones, ubiquitous in natural products. Initial investigations found that ZrCLj successfully catalyses the deprotection of 1,3-dioxane rings in compounds of type 4, assisted by microwave irradiation, leading to the formation 6-methoxytetrahydropyrans (5 and 6) (Scheme 1.2). 

A useful extension of this chemistry is that compounds 4 can be mono-deprotected and alkylated in a single pot (eq 4). Treatment of 4 with CsE in hot acetonitrile in the presence of an alkylating agent leads to SES-protected secondary amines 6 in high yields. 

An easy preparation of mono-deprotected thioglucopyranosides via a Candica cylindracea lipase-catalyzed selective hydrolysis of a commercially available per-acetylated precursor is described in Figure 3.22 [32], Ethyl 2,3,4-tri-O-acetyl-l-thio-P-D-glucopyranoside and ethyl 2,3,6-tri-O-acetyl-l-thio-p-D-glucopyrano-side were obtained in 100% and 54% isolated yields, respectively. 

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