Snider’s synthesis

Snider s synthesis of the aryl lignan skeleton is an example with stereochemistry.35 Either geometrical isomer (E or Z) of the starting material (l,4-diphenylbut-2-ene) was combined with formaldehyde and a mixed catalyst of MeAlCl2 and Me2AlCl. The all anti cyclised product 214 was formed in 40-50% yield. The first step must be a carbonyl ene reaction 212. It doesn t matter which way we write this as the molecule is symmetrical and we know that the stereochemistry is irrelevant. 

Scheme 13.22 Zftou and Snider s synthesis of pamafungin A and C models. Reagents and conditions a) h, HsIOg, 99% (1021) b) Mel, K2CO3, 69% (1022) c) Pd(OAc)2, S-Phos, K3PO4, 53% d) Zn, NH4CI, ultrasound e) MsCl, NEt3 f) Na2C03...

Fig. 69 Snider s synthesis of maldoxin and analogues of chloropestolide A and chloropupukeanolide D...

Another elegant example of the thermal generation and subsequent intramolecular cycloaddition of an o-QM can be found in Snider s biomimetic synthesis of the tetracyclic core of bisabosquals.2 Treatment of the starting material with acid causes the MOM ethers to cleave from the phenol core (Fig. 4.3). Under thermal conditions, a proton transfer ensues from one of the phenols to its neighboring benzylic alcohol residue. Upon expulsion of water, an o-QM forms. The E or Z geometry of the o-QM intermediate and its propensity toward interception by formaldehyde, water, or itself, again prove inconsequential as the outcome is decided by the relative thermodynamic stabilities among accessible products. 

Fig. 20 Summary of Snider s formal total synthesis of racemic guanacastepene (rac-187) (2002)...

As (—)-pulegone is not readily available, subsequent work addressed the natural enantiomer by different methods [12], but all completed their synthesis via Snider s enone (17). Asaoka utilised a TMS group as temporary directing volume (Scheme 5) [12a]. Cossy applied a photore-ductive cyclopropane ring opening, which was obtained by a diastereoselective Simmons-Smith reaction [12b]. Schmalz finally used a planar-chiral arene complex to synthesise enone 17 with interesting CrfCO), chemistry [12c]. 

Four total syntheses of FR901483 have been reported so far the enantiocontrolled approaches of Snider [2], Sorensen [5], and Ciufolini [6], and Funk s synthesis in the racemic series [7]. Furthermore, Brummond has communicated a partial total synthesis [8] and Wardrop reported a formal synthesis of the desmethylamino analog, which had been described by Snider [9,10]. Additionally, Kibayashi and Bonjoch and co-workers have reported other synthetic entries to the azatricyclic core of FR901483, which has also been reported by Brummond in her initial studies [11-14], An overview of FR901483 synthetic studies is outlined in Table 1. 

The synthesis of racemic desmethylamino FR901483 was reported by Snider in 1998 [9] (3.1.1). Three years later, using the A-alkoxy-A-acylnitrenium ion methodology for the azaspirocyclization step (3.2.1), Wardrop published a formal synthesis of desmethylamino FR901483 [10] having reached the advanced intermediate 15 previously reported in Snider s pioneering work (Scheme 8). 

Scheme 39. Snider s proposal for synthesis of TAN1251C and its relationship to the TAN 1251 alkaloids...

Scheme 13.20 Snider and Zhou s synthesis of the isoxazolone fragment. Reagents and conditions a) Pd(OAc)2, S-Phos, K3PO4, H2O (cat), toluene, reflux b) Zn, NH4CI, THF/MeOH/ H2O, sonication, 25°C c) MsCl, EtjN, CH2CI2, 0°C, 15 min d) NajCOj, 1 1 THF/H2O, 40 min...

Snider s group has also applied the reaction to the synthesis... 

The antitumor antibiotic phloeodictine A1 (171) has been synthesized by Snider s group (Scheme 15.37). The unstable azide derived from 167 was subjected to a polymer supported tandem Staudinger-aza-Wittig followed by a retro Diels-Alder reaction to afford intermediate 170. Addition of 11-dodecenyl magnesium bromide followed by alkylation reaction and deprotection completes an efficient synthesis of phloeodictine A1 (171). 

Two formal syntheses of unnatural 5-ep/-cermizine C (1160) are included for completeness (Scheme 149). Following Snider s procedure for the transformation of racemic pelletierine into ( )-5- -cermizine, ° Bosque et al. converted their chiral sulfinamide (- -)-1183 (cf Scheme 148) into (—)-pelletierine (1184), condensation of which with Meldrum s acid yielded the unconjugated bicyclic lactam (—)-1185. DiastereofaciaUy selective hydrogenation then afforded the saturated quinoHzidinone (—)-1186 (dr 13 1), which was converted in by-now famihar steps into the trifluoroacetate salt of (- -)-5- i-cermizine C. The approach of Chou et al. also converged with Snider s route when their racemic vinyl sulfide intermediate ( )-1107, previously used in the synthesis of (ih)-epimyrtine (rac-1098) (c Scheme 139 Section 4.7) was converted into (ib)-1187 upon treatment with excess methyUithium. ... 

The formal total synthesis of racemic guanacastepene (rac-187) from Snider and co-workers (Fig. 20) was submitted six months later than the completed synthesis of Danishefsky s group [116-118]. The shortest sequence developed by the Snider group utilized the sequential cuprate addition/enolate alkylation of 2-methylcyclopent-2-enone 90 previously exploited by Piers, Williams and Danishefsky (Schemes 15 and 31). As outlined in Figs. 19 and 20, the strategies of Danishefsky and Snider are closely related. Both rely on stepwise annulations to build up the tricyclic ring system. They differ only in respect to the particular reactions that converted the monocyclic starting material (90) via bicyclic hydroazulenes (207 vs 227) into the desired tricyclic 5-7-6-system (224). 

S.J. Danishefsky and co-workers developed a synthetic route to the neurotrophic illicinones and a total synthesis of the natural product tricycloillicinone. Illicinones were found to enhance the action of choline acetyltransferase, which catalyzes the synthesis of acetylcholine from its precursors. The application of Corey-Snider oxidative cycHzation and the Barton-McCombie radical deoxygenation provided a direct route to tricycloillicinone. 

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