**4. Conclusions**

In summary, the antimicrobial activity of five phenolic nor-triterpenes isolated from two *Maytenus* species and those of four derivatives revealed that compound 6 showed significant activity against Gram-positive bacteria, higher than cephotaxime, used as positive control. In order to understand and further optimize the structural requirements for e ffective inhibition of bacterial growth in vitro, an extensive SAR analysis of a series of nor-triterpene phenols was performed. This study suggests that the phenolic moiety and carboxyl group at C-4 on the A-ring, a nonconjugated double bond system on the B-ring, and the ring E, characteristic of pristimerin series, all contribute to the antimicrobial e ffectiveness. Based on these findings, we propose a hypothetical lead compound, 4-carboxy-6 α-hydroxy-pristimerol. This comprehensive SAR study supports the future rational design of antimicrobial agents based on the phenolic nor-triterpene sca ffold.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3417/9/15/2957/s1, Figures S1–S4: 1H and 13C NMR spectra of derivatives **6**–**9**.

**Author Contributions:** Conceptualization, L.M. and I.L.B.; methodology, L.M. and I.A.J.; investigation, M.R.L. and C.P.R.; data curation, L.M. and I.A.J.; writing-original draft preparation, I.L.B.; writing-review and editing, I.L.B. and L.M.; supervision, L.M. and I.L.B.; and funding acquisition, I.L.B.

**Funding:** This study was supported by SAF2015-65113-C2-1-R and RTI2018-094356-B-C21 Spanish MINECO co-funded by the European Regional Development Fund (FEDER) projects.

**Acknowledgments:** C.P.R. thanks the Cabildo de Tenerife (Agustín de Betancourt Program).

**Conflicts of Interest:** The authors declare no conflict of interest
