1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Organic & Supramolecular Chemistry Functionalized Pyrimidines from Alkynes and Nitriles: Application towards the Synthesis of Marine Natural Product Meridianin Analogs Banyangala Mohan, [a] Chettiyan Thodi F. Salfeena, [a, c] Kizhakkan T. Ashitha, [a, c] Gopika V. Krishnan, [b, c] Abdul Rasheed S. Jesmina, [b, c] Angela M. Varghese, [a] Siddappa A. Patil, [d] Bhaskaran Nair S. Dileep Kumar, [b, c] and Balappa S. Sasidhar* [a, c] Fully substituted pyrimidine synthesis accomplished from alkynes and nitriles via BF 3 . Et 2 O mediated [2 + 2 + 2] cyclo- addition. The substrate scope of the reaction was broad to include terminal alkynes to internal alkynes and aromatic nitriles to aliphatic nitriles furnished good to acceptable chemical yields. The marine alkaloid, meridianin analogs were synthesized successfully by utilizing this protocol. The pyrimi- dine analogues were also screened for their broad spectrum of antibacterial property against ten bacteria. Among the deriva- tives, 2,4-dimethyl-6-p-tolylpyrimidine (3b) has shown excellent inhibition potential against most of the tested organisms with a range of 9 to 21 mm zone of inhibition. Introduction Pyrimidines and their associated systems are widespread and play a significant role in chemical, pharmaceutical and Phyto- pharmaceuticals domains. [1] For instance, among the Meridia- nins (A À G) isolated from the tunicate Aplidium meridianum, Meridianin D showed cytotoxicity against a variety of tumour cell lines. [2] Meridianins (A À F) were found to inhibit CDKs, GSK- 3, PKA and other protein kinases in micro-molar concentra- tion. [3] Another pyrimidine core of natural origin, Heteromine (F À H) isolated from the Heterostemma brownie Hay has been well reported for its cytotoxicity in several cell lines. [4] Besides several synthetic pyrimidines have been shown to display critical biological properties. [1,5] Etravirine and Rilpivirine are the two non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are approved by the US Food and Drug Administration (FDA) and are currently available for the treatment of AIDS. [6] 2- Amino-4-hydroxy pyrimidines are found to be antifolates (antagonists of folic acid). Their tri-substituted pyrimidine derivative, Iclaprim, which is rationally designed, was found to be active against methicillin-, TMP-, and vancomycin-resistant strains. [7] And tetra-substituted pyrimidine; pyrimethamine is a selective inhibitor of the DHFR of malarial plasmodia (Fig- ure 1). [8] Considering the importance of pyrimidine moieties in various applications, several synthetic methods have been reported [9] e.g., the classical Pinner [9a] and Bredereck [9b] syn- thesis, involving cyclocondensation of 1,3-dicarbonyl com- pounds with amidines and formamide, respectively. Martinez et al. showed condensation of carbonyl compounds with nitriles catalyzed by triflic anhydride is also well explored. [9c] Another well-known protocol for 2-amino pyrimidines is base catalyzed cyclocondensation of chalcones and thiourea. [10] Kim et al. reported 2,4,6-trisubstituted pyrimidines from Baylis Hill- man adducts and amidines, [11] where the preparation of the starting materials is not an easy task always. The [2 + 2 + 2] [a] B. Mohan, C. T. F. Salfeena, K. T. Ashitha, A. M. Varghese, Dr. B. S. Sasidhar Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram - 695 019, Kerala, India E-mail: drsasidharbs@niist.res.in [b] G. V. Krishnan, A. R. S. Jesmina, Dr. B. N. S. D. Kumar Agro-Processing and Technology Division, CSIR –NIIST, Thir- uvananthapuram - 695 019, Kerala, India [c] C. T. F. Salfeena, K. T. Ashitha, G. V. Krishnan, A. R. S. Jesmina, Dr. B. N. S. D. Kumar, Dr. B. S. Sasidhar Academy of Scientific and Innovative Research (AcSIR), CSIR-NIIST, Thir- uvananthapuram - 695 019, Kerala, India [d] Dr. S. A. Patil Centre for Nano and Material Sciences, Jain University, Jain Global Cam- pus, Kanakapura, Ramanagaram, Bangalore - 562112, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201801126 Figure 1. Bioactives with pyrimidine core. Communications DOI: 10.1002/slct.201801126 6394 ChemistrySelect 2018, 3, 6394 – 6398  2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim