Compare the epidemiological and clinical features of imported and local COVID-19 cases in Hainan, China.

BACKGROUND: Effective management of imported cases is an important part of epidemic prevention and control. Hainan Province, China reported 168 coronavirus disease 2019 (COVID-19), including 112 imported cases on February 19, 2020, but successfully contained the epidemic within 1 month. We described the epidemiological and clinical characteristics of COVID-19 in Hainan and compared these features between imported and local cases to provide information for other international epidemic areas. METHODS: We included 91 patients (56 imported and 35 local cases) from two designated hospitals for COVID-19 in Haikou, China, from January 20 to February 19, 2020. Data on the demographic, epidemiological, clinical and laboratory characteristics were extracted from medical records. Patients were followed until April 21, 2020, and the levels of antibodies at the follow-ups were also analysed by the Wilcoxon matched-pairs signed ranks test. RESULTS: Of the 91 patients, 78 (85.7%) patients were diagnosed within the first three weeks after the first case was identified (Day 1: Jan 22, 2020), while the number of local cases started to increase during the third week. No new cases occurred after Day 29. Fever and cough were two main clinical manifestations. In total, 15 (16.5%) patients were severe, 14 (15.4%) had complicated infections, nine (9.9%) were admitted to the intensive care unit, and three died. The median duration of viral shedding in feces was longer than that in nasopharyngeal swabs (19 days vs 16 days, P = 0.007). Compared with local cases, imported cases were older and had a higher incidence of fever and concurrent infections. There was no difference in outcomes between the two groups. IgG was positive in 92.8% patients (77/83) in the follow-up at week 2 after discharge, while 88.4% patients (38/43) had a reduction in IgG levels in the follow-up at week 4 after discharge, and the median level was lower than that in the follow-up at week 2 (10.95 S/Cut Off (S/CO) vs 15.02 S/CO, P <  0.001). CONCLUSION: Imported cases were more severe than local cases but had similar prognoses. The level of IgG antibodies declined from week 6 to week 8 after onset. The short epidemic period in Hainan suggests that the epidemic could be quickly brought under control if proper timely measures were taken.

Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin.

A stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, 8-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.

The domestication of ortho-quinone methides.

CONSPECTUS: An ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature. About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a magnesium phenoxide that we supposed underwent ß-elimination of the transferred Boc residue to form an o-QM for immediate further reactions. Moreover, the cascade proved controllable through careful manipulation of metallic and temperature levers so that it could be paused, stopped, or restarted at various intermediates and stages. This new level of domestication enabled us to deploy o-QMs for the first time in a range of applications including diastereocontrolled reactions. This sequence ultimately could be performed in either multipot or single pot processes. The subsequent reaction of the fleeting o-QM intermediates included the 1,4-conjugate additions that led to unbranched or branched ortho-alkyl substituted phenols and Diels-Alder reactions that provided 4-unsubstituted or 4-substituted benzopyrans and chroman ketals. The latter cycloadducts were obtained for the first time with outstanding diastereocontrol. In addition, the steric effects of the newly created stereocenters in subsequent reactions of chroman ketals and acetals were studied and proved predictable. Through the use of a chiral auxiliary, Diels-Alder products were deployed in numerous enantioselective reactions including several complex natural products syntheses. In this Account, we summarize our efforts, which we hope have contributed to the synthetic renaissance for this venerable species.

A new strategy for detection and development of tractable telomerase inhibitors.

Despite intense academic and industrial efforts and innumerable in vitro and cell studies, no small-molecule telomerase inhibitors have emerged as drugs. Insufficient understanding of enzyme structure and mechanisms of interdiction coupled with the substantial complexities presented by its dimeric composition have stalled all progress toward small-molecule therapeutics. Here we challenge the assumption that human telomerase provides the best platform for inhibitor development by probing a monomeric Tetrahymena telomerase with six tool compounds. We find BIBR-1532 (2) and MST-312 (5) inhibit only human telomerase, whereas ß-R (1), THyF (3), TMPyP4 (6), and EGCG (4) inhibit both enzymes. Our study demonstrates that some small-molecule scaffolds can be easily surveyed with in vitro studies using Tetrahymena telomerase, a finding that could lead to more tractable inhibitors with a greater potential for development given the more precise insights that can be gleaned from this more easily expressed and assayed monomeric enzyme.

A convergent total synthesis of (±)-γ-rubromycin.

An expeditious convergent total synthesis affords (±)-γ-rubromycin (1) in 4.4% overall yield. The longest linear sequence is 12 steps from commercial starting materials. The effort highlights a remarkable late-stage oxidative [3 + 2] cycloaddition for construction of the spiroketal, a regioselective carbonyl methylenation, a boron tribromide promoted deprotection, ortho- to para- naphthoquinone spiroketal rearrangement, and a tautomerization sequence.

Diastereoselective syntheses of chroman spiroketals via [4 + 2] cycloaddition of enol ethers and o-quinone methides.

A variety of chroman spiroketals are synthesized via inverse-demand [4 + 2] cycloaddition of enol ethers and ortho-quinone methides (o-QMs). Low temperature o-QM generation in situ allows for the kinetic, diastereoselective construction of these motifs, providing entry to a number of unusual chroman spiroketal natural products.

Facile synthesis of naphthoquinone spiroketals by diastereoselective oxidative [3 + 2] cycloaddition.

A highly selective oxidative [3 + 2] cycloaddition of chiral enol ethers and hydroxynaphthoquinone is described. This convergent strategy is amenable to an enantioselective synthesis of beta-rubromycin and related naphthoquinone spiroketals. Several compounds were found to inhibit DNA-polymerase and telomerase in a manner resembling alpha-rubromycin and beta-rubromycin.

Synthesis of electron deficient 5,6-aryloxy spiroketals.

[reaction: see text] A strategy for the construction of electron deficient 5,6-aryloxy spiroketal is reported. The process should prove useful for the synthesis of natural products containing similar spiroketals. The strategy uncovers an unexpected rearrangement between ortho and para quinone spiroketals.