Chemical Etiology of Nucleic Acid Structure: The Pentulofuranosyl Oligonucleotide Systems: The (1′→3′)‐β‐L‐Ribulo, (4′→3′)‐α‐L‐Xylulo,and (1′→3′)‐α‐L‐Xylulo Nucleic Acids

Under potentially prebiotic scenarios, ribose (pentose), the component of RNA is formed in meager amounts, as opposed to ribulose and xylulose (pentuloses). Consequently, replacement of ribose in RNA, with pentulose sugars, gives rise to prospective oligonucleotide candidates that are potentially prebiotic structural variants of RNA that could be formed by the same type of chemical pathways that gave rise to RNA from ribose. The potentially natural alternative (1′→3′)‐ribulo oligonucleotides and (4′→3′)‐ and (1′→3′)‐xylulo oligonucleotides consisting of adenine and thymine were synthesized and found to exhibit no self‐pairing or cross‐pairing with RNA. This signifies that even though pentulose sugars may have been abundant in a prebiotic scenario, the pentulose nucleic acids (NAs), if and when formed, would not have been competitors of RNA, or interfered with the emergence of RNA as a functional informational system. The reason for the lack of base pairing in pentulose NA highlights the contrasting and central role played by the furanosyl ring in RNA and pentulose NA, enabling and optimizing the base pairing in RNA, while impeding it in pentulose NA.     

Functionalization of 2″‐C‐(Piperazinomethyl)‐2′,3′‐BcNA (Bicyclic Nucleic Acids) with Pyren‐1‐ylcarbonyl Units

Herein, we describe the incorporation of 2″‐C‐(piperazinomethyl)‐2′,3′‐BcNA (Bicyclic Nucleic Acids) into oligonucleotides via phosphoramidite chemistry and their subsequent solid‐phase functionalization with pyren‐1‐ylcarbonyl units after oligonucleotide synthesis. Thermal denaturation measurements showed that one modification led to increased thermal stability of the resulting duplex, and that two modifications could be incorporated in close proximity without decreasing the duplex stability (compared to the duplex stability of unmodified RNA). Fluorescence studies of the modified duplexes revealed that the structure and intensity of the fluorescence spectra were largely sequence‐dependent. Furthermore, molecular‐modeling studies showed that the pyrene moieties are placed in the major groove, and that the configuration at C(2″) is important for the thermal stability of the duplex.     

Three different fluoro‐ or chloro‐substituted 1′‐deoxy‐1′‐phenyl‐β‐D‐ribofuranoses

Crystal structures are reported for three fluoro‐ or chloro‐substituted 1′‐deoxy‐1′‐phenyl‐β‐D‐ribofuranoses, namely 1′‐deoxy‐1′‐(2,4,5‐trifluorophenyl)‐β‐D‐ribofuranose, C₁₁H₁₁F₃O₄, (I), 1′‐deoxy‐1′‐(2,4,6‐trifluorophenyl)‐β‐D‐ribofuranose, C₁₁H₁₁F₃O₄, (II), and 1′‐(4‐chlorophenyl)‐1′‐deoxy‐β‐D‐ribofuranose, C₁₁H₁₃ClO₄, (III). The five‐membered furanose ring of the three compounds has a conformation between a C2′‐endo,C3′‐exo twist and a C2′‐endo envelope. The ribofuranose groups of (I) and (III) are connected by intermolecular O—H...O hydrogen bonds to six symmetry‐related molecules to form double layers, while the ribofuranose group of (II) is connected by O—H...O hydrogen bonds to four symmetry‐related molecules to form single layers. The O...O contact distance of the O—H...O hydrogen bonds ranges from 2.7172 (15) to 2.8895 (19) Å. Neighbouring double layers of (I) are connected by a very weak intermolecular C—F...π contact. The layers of (II) are connected by one C—H...O and two C—H...F contacts, while the double layers of (III) are connected by a C—H...Cl contact. The conformations of the molecules are compared with those of seven related molecules. The orientation of the benzene ring is coplanar with the H—C1′ bond or bisecting the H—C1′—C2′ angle, or intermediate between these positions. The orientation of the benzene ring is independent of the substitution pattern of the ring and depends mainly on crystal‐packing effects.     

Synthesis of novel α,α′,β-trisubstituted β-lactones

A concise and efficient synthesis of α,α′,β-trisubstituted β-lactones is presented. These novel lactones are easily obtained in five steps and will be dedicated to anionic ring opening polymerization.