## 4 Chemical Synthesis of Rice Phytoalexins
### Phytocassane Chemical Synthesis  
(\(-\))-Phytocassane D was synthesized from the (\(R\))-Wieland-Miescher ketone **1** (Scheme 1) and, after a comparison with the spectral data of the authentic natural product, its absolute configuration was confirmed as _ent_-cassane (Table 3, entry 2) [144]. Figure 12: Biosynthesis of phenylamides and Sakuranetin. Multiple arrows indicate multiple enzymatic steps. E4P: erythrose 4-phosphate; PEP: phosphoenol pyruvate; T5H: tryptamine 5-hydroxylase (EC 1.14.-. ); TDC: L-tryptophan decarboxylase (aromatic-L-amino-acid decarboxylase, EC 4.1.1.28); TYDC: L-tyrosine decarboxylase (EC 4.1.1.25) (adapted from [21]). \begin{table}
\begin{tabular}{l l l l} \hline \hline
**Entry** & **Compound** & **Skeletal Type** & **References** \\ \hline
1 & (\(\pm\))-Momilactone A & (9\(\beta\)-H)-Pimarane & [143] \\ \hline
2 & (\(-\))-Phytocassane D & _ent_-Cassane & [144] \\ \hline
3 & (\(+\))-Oryzalexin A, B and C & _ent_-Isopimarane & [145] \\ \hline
4 & (\(-\))-Sakuranetin & Flavanone & [146; 147] *, \\ \hline
5 & (\(\pm\))-Sakuranetin & Flavanone & [148; 150; 151] *, \\  & & [151], [152; 153; 154; 155] * \\ \hline \hline \end{tabular}  
* Semisynthesis of Sakuranetin from naringenin.  
\end{table} 
Table 3: Rice phytoalexin chemical synthesis. Compound **1** was converted into **2** through a six steps sequence where two methyl groups on C-(4) were inserted. A Robinson annulation of **2** gave the unsaturated tricyclic ketone **3** that was converted into **4** by passing through the saturated tricyclic ketone and inserting the double bond by employing a sulfinate ester. Compound **4** was reacted with Me\({}_{2}\)CuLi to give, after a medium-pressure liquid chromatography, compound **5** in a discrete yield. The latter was converted into **6** using a four-step sequence that consisted of a formy- lation reaction, a subsequent sodium borohydride reduction, protection of the primary hydroxy group as a tert-butyldiphenylsilyl ether, and finally, a reoxidation of the secondary hydroxy group at C-(12) with PCC. Alkene **7** was obtained with a Shapiro reaction on ketone **6** followed by selective silyl-group deprotection. The double bond in compound **7** was transformed into an epoxy group, while the hydroxyl function was oxidized, yielding an  
Figure 1: (–)-Phytocassane D chemical synthesis [144]. Reagents and conditions: (a) (i) 2,2-dimethyl-1,3-propanolid, BF\({}_{3}\),Et\({}_{2}\)O; (ii) PhSH, aq, CH\({}_{2}\)O, Et\({}_{3}\)N, EtOH; (iii) Li, liq. NH\({}_{3}\), H\({}_{2}\)O, THF, then Mel, THF; (iv) LiAlH\({}_{4}\), THF; (v) aq. HCl, THF; (vi) TBSCI, imidazole, DMF (40%, 6 steps). (b) (i) NaH, HCO\({}_{2}\)Et, THF, PhMe; (ii) MeCOCH=CH\({}_{2}\), Et\({}_{3}\)N; (iii) NaOMe, MeOH (78%, 3 steps). (c) (i) Li, liq. NH\({}_{3}\), EtOH, THF; (ii) PCC, 3-A MS, CH\({}_{2}\)Cl\({}_{2}\); (iii) KH, PhSO\({}_{2}\)Me, THF; (iv) CaCO\({}_{3}\), PhMe, heat (77%, 4 steps). (d) (i) Me\({}_{2}\)CuLi, Et\({}_{2}\)O; (ii) diastereoisomer separation (47%). (e) (i) NaH, HCO\({}_{2}\)Et, MeOH; (ii) NaBH\({}_{4}\), THF, MeOH; (iii) TBDPSCI, imidazole, DMF; (iv) PCC, 4-Å MS, CH\({}_{2}\)Cl\({}_{2}\) (57%, 4 steps). (f) (i) TsNHNH\({}_{2}\), MgSO\({}_{4}\), PPTS, THF; (ii) excess LDA, THF then quenched with aq. NH\({}_{4}\)Cl; (iii) TBAF, THF, room temp. (68%, 3 steps). (g) (i) MCPBA, NaHCO\({}_{3}\), CHCl\({}_{3}\); (ii) Dess–Martin periodinane, CH\({}_{2}\)Cl\({}_{2}\); (iii) pyrrolidine, Et\({}_{2}\)O (67%, 3 steps). (h) (i) Ph\({}_{3}\)=CH\({}_{2}\), THF; (ii) Ac\({}_{2}\)O, DMAP, C\({}_{5}\)H\({}_{5}\)N; (iii) TBAF, THF; 50–60 \({}^{\circ}\)C; (iv) PCC, 4-Å MS, CH\({}_{2}\)Cl\({}_{2}\) (59%, 4 steps). (i) (i) LiHMDS, TMSCI, THF; (ii) MCPBA, NaHCO\({}_{3}\), hexane; (iii) (CO\({}_{2}\)H)\({}_{2}\), MeOH; (iv) Dess–Martin periodinane, CH\({}_{2}\)Cl\({}_{2}\); (v) TBSCI, imidazole, DMF (25%, 5 steps). (l) LiAlH\({}_{4}\), THF, then aq. HCl (64%). (k) TPAP, 4-ÅMS, MeCN, CH\({}_{2}\)Cl\({}_{2}\) (40%).