Nicolaou’s total synthesis

I11 Nicolaou s total synthesis of brevetoxin B, for example, out of the eleven transfused six- to eight-membered cyclic ethers, THP rings B, F, G, and I are constructed by application of this methodology through cydization of the appropriate... 

Fig. 6. Nicolaou s total synthesis construction of the maleic anhydride moiety. KHMDS = potassium hexamethyldisilazide, DIBAL = diisobutyl-aluminium hydride, acac = acetylacetonate, Ms = methanesulfonyl.

Fig. 7. Nicolaou s total synthesis oxidation to the y-hydroxy lactol. PDC = pyridinium dichromate, DMP = Dess-Martin periodinane.

Fig. 8. Nicolaou s total synthesis ketalization and homologation of the carboxylic acid side chain. TFA = trifluoroacetic acid, EDC = l-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride, DMAP = 4-(/V,/ /-dimethylamino)pyridine.

Nicolaou s total synthesis of the enediyne antibiotic, calicheamicin 71 [19], (Scheme 12.15 to Scheme 12.19) involves several new aspects in carbohydrate chemistry. The calicheamicin 71 oligosaccharide synthesis began with the construction of the D-ring intermediate from L-rhamnose. Thus, L-rhamnose 112 was converted into the glycosyl donor, trichloroacetimidate 118, through the... 

Nicolaou s total synthesis of a marine antitumor agent, eleutherobin [22] (Scheme 12.24), involves the attachment of D-arabinose to the aglycon intermediate. Thus, the glycosidation of the (-F )-carvone-derived hydroxy aldehyde 210 and the trichloroacetimidate 211, derived from... 

Paquette reacted secondary alcohol 70 with Martin s sulfurane to furnish cyclohexene 71 in 78% yield.35 In Nicolaou s total synthesis of eveminomicin 13,384-1, he created several dihydropyrans from anti elimination of the corresponding secondary alcohols.36 For example, alcohol 72 provides alkene 73 upon exposure to Martin s sulfurane and triethylamine in hot chloroform. 

Scheme 3. New directions in organic synthesis ring-closing metathesis as a key step in Nicolaou s total synthesis of coleophomones C and B (46 and 47).

Scheme 24. Final stages and completion of Nicolaou s total synthesis of swinholide A (1).

Scheme 8. First example of cheletropic elimination of SO2 for o-quinodimethane generation (a), and application of the strategy as the key step in Nicolaou s total synthesis of estra-1,3,5(10)-trien-17-one (b).

Scheme 14.2 Nicolaou s total synthesis of hirsutellone B (12) via domino epoxide open-ing/[4 + 2]-cycloaddition.

Scheme 37 Early stage enamine-catalyzed Michael addition in Nicolaou s total synthesis of biyouyanagin A (156)...

Similar tandem Aldol/Oxa-Michael/Aldol/Lactonization reactions have been reported in literatures, which include Prof. Nicolaou s total synthesis research of cortistatin A [28, 29]. 

Solid Phase chemistry has also been used to help solving this problem by immobilizing one of the partners (organic electrophile or organostannane) on the solid support to help purification. An example of this approach is found in Nicolaou s total synthesis of (S)-zearalenone (43 — 44). 

SCHEME 1.11 Biomimetic and conventional strategies toward hirsutellones Nicolaou s total synthesis was not originally reported as bio-mimetic but supports the proposed tail-to-head biosynthetic pathway Uchiro reported a conventional total synthesis we reported a biomimetic formal synthesis leading to Nicolaou s intermediate, supporting the head-to-tail biosynthetic pathway. 

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