A Sulfuryl Group Transfer Strategy to Selectively Prepare Sulfated Steroids and Isotopically Labelled Derivatives

The treatment of common steroids: estrone, estradiol, cortisol, and pregnenolone with tributylsulfoammonium betaine (TBSAB) provides a convenient chemoselective conversion of the steroids alcohol/phenol moiety to the corresponding steroidal organosulfate. An important feature of the disclosed methodology is the millimolar scale of the reaction, and the isolation of the corresponding steroid sulfates as their biologically relevant sodium salts without the need for ion-exchange chromatography. The scope of the method was further explored in the estradiol and pregnanediol steroid systems with the bis-sulfated derivatives. Ultimately, a method to install an isotopic label, deuterium (2H) combined with estrone sulfation is a valuable tool for its mass-spectrometric quantification in biological studies.

Clinical outcomes for Day 3 double cleavage-stage embryo transfers versus Day 5 or 6 single blastocyst transfer in frozen–thawed cycles: a retrospective comparative analysis

Objective This study aimed to compare the clinical outcomes for transfer of Day 3 (D3) double cleavage-stage embryos and Day 5/6 (D5/6) single blastocysts in the frozen embryo transfer (FET) cycle to formulate a more appropriate embryo transplantation strategy. Methods We retrospectively analyzed 609 FET cycles from 518 women from April 2017 to March 2021. All FETs were assigned to the D3-DET group (transfer of a Day 3 double cleavage-stage embryo), D5-SBT group (transfer of a Day 5 single blastocyst), or D6-SBT group (transfer of a Day 6 single blastocyst). Clinical outcomes were comparatively analyzed. Results There were no significant differences in the biochemical pregnancy rate, clinical pregnancy rate, or ongoing pregnancy rate between the D3-DET and D5-SBT groups, but these rates in the two groups were all significantly higher compared with those in the D6-SBT group. The implantation rate in the D5-SBT group was significantly higher than that in the D3-DET group. The twin pregnancy rate in the D5-SBT and D6-SBT groups was significantly lower than that in the D3-DET group. Conclusion This study suggests that D5-SBT is the preferred option for transplantation. D6-SBT reduces the pregnancy rate, making it a more cautious choice for transfer of such embryos.

Synthesis of O6-alkylated preQ1 derivatives

A naturally occurring riboswitch can utilize 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d]pyrimidines starting from readily accessible N2-pivaloyl-protected 6-chloro-7-cyano-7-deazaguanine. Substitution of the 6-chloro atom with the alcoholate of interest proceeds straightforward. The transformation of the 7-cyano substituent into the required aminomethyl group turned out to be challenging and was solved by a hydration reaction sequence on a well-soluble dimethoxytritylated precursor via in situ oxime formation. The synthetic path now provides a solid foundation to access O6-alkylated 7-aminomethyl-7-deazaguanines for the development of RNA labeling tools based on the preQ1 class-I riboswitch scaffold.